@erosolaraijs/cure 1.0.6 → 2.1.0

package/dist/capabilities/cancerTreatmentCapability.js

@@ -277,7 +277,418 @@ export class CancerTreatmentCapabilityModule {
             cancerTypes: ['Multiple Myeloma'],
             approvedDrugs: ['Idecabtagene vicleucel', 'Ciltacabtagene autoleucel', 'Teclistamab'],
             mechanismOfAction: 'CAR-T/bispecific targets BCMA on myeloma cells',
-            evidenceLevel: 'FDA-Approved', biomarker: 'BCMA+ multiple myeloma' }
+            evidenceLevel: 'FDA-Approved', biomarker: 'BCMA+ multiple myeloma' },
+        // === ADDITIONAL BISPECIFIC ANTIBODY TARGETS ===
+        { gene: 'CD20xCD3', protein: 'CD20 x CD3 Bispecific', pathway: 'Bispecific T-cell Engager',
+            cancerTypes: ['DLBCL', 'Follicular Lymphoma', 'CLL', 'Mantle Cell Lymphoma', 'Marginal Zone Lymphoma'],
+            approvedDrugs: ['Mosunetuzumab', 'Epcoritamab', 'Glofitamab'],
+            mechanismOfAction: 'Bispecific engages T-cells to kill CD20+ B-cells',
+            evidenceLevel: 'FDA-Approved', biomarker: 'CD20+ B-cell lymphoma' },
+        { gene: 'GPRCxCD3', protein: 'GPRC5D x CD3 Bispecific', pathway: 'Bispecific T-cell Engager',
+            cancerTypes: ['Multiple Myeloma'],
+            approvedDrugs: ['Talquetamab'],
+            mechanismOfAction: 'Bispecific targets GPRC5D on myeloma cells',
+            evidenceLevel: 'FDA-Approved', biomarker: 'GPRC5D+ myeloma' },
+        { gene: 'FcRHxCD3', protein: 'FcRH5 x CD3 Bispecific', pathway: 'Bispecific T-cell Engager',
+            cancerTypes: ['Multiple Myeloma'],
+            approvedDrugs: ['Cevostamab (investigational)'],
+            mechanismOfAction: 'Bispecific targets FcRH5 on myeloma cells',
+            evidenceLevel: 'Phase II', biomarker: 'FcRH5+ myeloma' },
+        { gene: 'DLL3xCD3', protein: 'DLL3 x CD3 Bispecific', pathway: 'Bispecific T-cell Engager',
+            cancerTypes: ['SCLC', 'Neuroendocrine'],
+            approvedDrugs: ['Tarlatamab'],
+            mechanismOfAction: 'Bispecific targets DLL3 on SCLC cells',
+            evidenceLevel: 'FDA-Approved', biomarker: 'DLL3+ SCLC' },
+        { gene: 'HER2xCD3', protein: 'HER2 x CD3 Bispecific', pathway: 'Bispecific T-cell Engager',
+            cancerTypes: ['Breast', 'Gastric', 'NSCLC'],
+            approvedDrugs: ['Zanidatamab (investigational)'],
+            mechanismOfAction: 'Bispecific targets HER2+ tumors',
+            evidenceLevel: 'Phase II', biomarker: 'HER2+ solid tumors' },
+        // === ADDITIONAL ADC TARGETS ===
+        { gene: 'FRa', protein: 'Folate Receptor Alpha', pathway: 'Targeted Delivery',
+            cancerTypes: ['Ovarian', 'NSCLC', 'Endometrial'],
+            approvedDrugs: ['Mirvetuximab Soravtansine'],
+            mechanismOfAction: 'FRα-targeting ADC delivers DM4 payload',
+            evidenceLevel: 'FDA-Approved', biomarker: 'FRα high expression' },
+        { gene: 'CEACAM5', protein: 'Carcinoembryonic Antigen', pathway: 'Targeted Delivery',
+            cancerTypes: ['Colorectal', 'Gastric', 'Pancreatic', 'NSCLC'],
+            approvedDrugs: ['Tusamitamab Ravtansine (investigational)'],
+            mechanismOfAction: 'CEACAM5-targeting ADC',
+            evidenceLevel: 'Phase III', biomarker: 'CEACAM5+ tumors' },
+        { gene: 'B7H4', protein: 'B7 Homolog 4', pathway: 'Targeted Delivery',
+            cancerTypes: ['Breast', 'Ovarian', 'Endometrial'],
+            approvedDrugs: ['AZD8205 (investigational)'],
+            mechanismOfAction: 'B7H4-targeting ADC',
+            evidenceLevel: 'Phase I', biomarker: 'B7H4+ tumors' },
+        { gene: 'c-MET ADC', protein: 'c-MET ADC Target', pathway: 'Targeted Delivery',
+            cancerTypes: ['NSCLC', 'Gastric', 'RCC'],
+            approvedDrugs: ['Telisotuzumab Vedotin (investigational)'],
+            mechanismOfAction: 'c-MET-targeting ADC delivers MMAE',
+            evidenceLevel: 'Phase II', biomarker: 'c-MET high tumors' },
+        // === RADIOLIGAND THERAPY TARGETS ===
+        { gene: 'SSTR2', protein: 'Somatostatin Receptor Type 2', pathway: 'Radioligand Therapy',
+            cancerTypes: ['GI NET', 'Pancreatic NET', 'Pheochromocytoma', 'Paraganglioma'],
+            approvedDrugs: ['177Lu-DOTATATE (Lutathera)'],
+            mechanismOfAction: 'Peptide receptor radionuclide therapy',
+            evidenceLevel: 'FDA-Approved', biomarker: 'SSTR+ neuroendocrine tumors' },
+        { gene: 'FAP', protein: 'Fibroblast Activation Protein', pathway: 'Radioligand Therapy',
+            cancerTypes: ['Pancreatic', 'Breast', 'Colorectal', 'Sarcoma', 'All Solid Tumors'],
+            approvedDrugs: ['177Lu-FAP-2286 (investigational)', '225Ac-FAPI (investigational)'],
+            mechanismOfAction: 'FAP-targeted radioligand therapy',
+            evidenceLevel: 'Phase II', biomarker: 'FAP+ tumor stroma' },
+        { gene: 'CXCR4', protein: 'C-X-C Chemokine Receptor Type 4', pathway: 'Radioligand Therapy',
+            cancerTypes: ['Multiple Myeloma', 'AML', 'CLL', 'Lymphoma'],
+            approvedDrugs: ['177Lu-pentixather (investigational)'],
+            mechanismOfAction: 'CXCR4-targeted radioligand therapy',
+            evidenceLevel: 'Phase II', biomarker: 'CXCR4+ hematologic malignancies' },
+        // === PEDIATRIC CANCER TARGETS ===
+        { gene: 'GD2', protein: 'Disialoganglioside GD2', pathway: 'Immunotherapy Target',
+            cancerTypes: ['Neuroblastoma', 'Osteosarcoma', 'Ewing Sarcoma', 'Melanoma'],
+            approvedDrugs: ['Dinutuximab', 'Naxitamab'],
+            mechanismOfAction: 'Anti-GD2 antibody mediates ADCC',
+            evidenceLevel: 'FDA-Approved', biomarker: 'GD2+ tumors' },
+        { gene: 'MYCN', protein: 'N-Myc Proto-Oncogene', pathway: 'Transcription Factor',
+            cancerTypes: ['Neuroblastoma', 'Medulloblastoma', 'Rhabdomyosarcoma'],
+            approvedDrugs: ['Aurora A inhibitors (investigational)', 'BET inhibitors (investigational)'],
+            mechanismOfAction: 'Indirect MYCN destabilization',
+            evidenceLevel: 'Phase II', biomarker: 'MYCN amplification' },
+        { gene: 'PAX-FOXO1', protein: 'PAX3/7-FOXO1 Fusion', pathway: 'Fusion Oncoprotein',
+            cancerTypes: ['Rhabdomyosarcoma (alveolar)'],
+            approvedDrugs: ['Investigational agents'],
+            mechanismOfAction: 'Target fusion-driven transcription',
+            evidenceLevel: 'Phase I', biomarker: 'PAX-FOXO1 fusion' },
+        { gene: 'EWS-FLI1', protein: 'EWSR1-FLI1 Fusion', pathway: 'Fusion Oncoprotein',
+            cancerTypes: ['Ewing Sarcoma'],
+            approvedDrugs: ['Lurbinectedin', 'Trabectedin', 'TK216 (investigational)'],
+            mechanismOfAction: 'Target EWS-FLI1 fusion protein activity',
+            evidenceLevel: 'Phase II', biomarker: 'EWS-FLI1 fusion' },
+        { gene: 'SHH', protein: 'Sonic Hedgehog Pathway', pathway: 'Hedgehog',
+            cancerTypes: ['Medulloblastoma', 'Basal Cell Carcinoma'],
+            approvedDrugs: ['Vismodegib', 'Sonidegib'],
+            mechanismOfAction: 'SMO inhibition blocks Hedgehog signaling',
+            evidenceLevel: 'FDA-Approved', biomarker: 'SHH-activated tumors' },
+        { gene: 'WT1', protein: 'Wilms Tumor 1', pathway: 'Transcription Factor',
+            cancerTypes: ['Wilms Tumor', 'AML', 'Mesothelioma'],
+            approvedDrugs: ['WT1 vaccines (investigational)', 'WT1-TCR T-cells (investigational)'],
+            mechanismOfAction: 'Immune targeting of WT1+ cells',
+            evidenceLevel: 'Phase II', biomarker: 'WT1 overexpression' },
+        // === ULTRA-RARE CANCER TARGETS ===
+        { gene: 'SS18-SSX', protein: 'SS18-SSX Fusion', pathway: 'Fusion Oncoprotein',
+            cancerTypes: ['Synovial Sarcoma'],
+            approvedDrugs: ['Trabectedin', 'Pazopanib', 'SYD985 (investigational)'],
+            mechanismOfAction: 'Target SS18-SSX driven transcription',
+            evidenceLevel: 'Phase II', biomarker: 'SS18-SSX fusion' },
+        { gene: 'MDM2', protein: 'Mouse Double Minute 2', pathway: 'p53 Pathway',
+            cancerTypes: ['Liposarcoma', 'Glioblastoma', 'AML'],
+            approvedDrugs: ['Milademetan (investigational)', 'Idasanutlin (investigational)'],
+            mechanismOfAction: 'MDM2 inhibition restores p53 activity',
+            evidenceLevel: 'Phase II', biomarker: 'MDM2 amplification, wild-type TP53' },
+        { gene: 'CDK12', protein: 'Cyclin-Dependent Kinase 12', pathway: 'DNA Repair',
+            cancerTypes: ['Prostate', 'Ovarian'],
+            approvedDrugs: ['PARP inhibitors', 'Platinum chemotherapy', 'Immunotherapy'],
+            mechanismOfAction: 'CDK12 loss creates genomic instability',
+            evidenceLevel: 'FDA-Approved', biomarker: 'CDK12 biallelic loss' },
+        { gene: 'NF1', protein: 'Neurofibromin', pathway: 'RAS/MAPK',
+            cancerTypes: ['MPNST', 'Glioma', 'Melanoma', 'NSCLC'],
+            approvedDrugs: ['Selumetinib', 'MEK inhibitors'],
+            mechanismOfAction: 'MEK inhibition for NF1-driven RAS activation',
+            evidenceLevel: 'FDA-Approved', biomarker: 'NF1 loss/mutation' },
+        { gene: 'NF2', protein: 'Merlin/Neurofibromin 2', pathway: 'Hippo Pathway',
+            cancerTypes: ['Meningioma', 'Schwannoma', 'Mesothelioma'],
+            approvedDrugs: ['Bevacizumab', 'FAK inhibitors (investigational)'],
+            mechanismOfAction: 'Target downstream effectors of NF2 loss',
+            evidenceLevel: 'Phase II', biomarker: 'NF2 mutation/loss' },
+        { gene: 'SDH', protein: 'Succinate Dehydrogenase', pathway: 'Metabolic',
+            cancerTypes: ['Pheochromocytoma', 'Paraganglioma', 'GIST', 'RCC'],
+            approvedDrugs: ['Temozolomide', 'Belzutifan'],
+            mechanismOfAction: 'Target pseudohypoxia pathway',
+            evidenceLevel: 'FDA-Approved', biomarker: 'SDH-deficient tumors' },
+        { gene: 'VHL', protein: 'Von Hippel-Lindau', pathway: 'HIF/VEGF',
+            cancerTypes: ['Clear Cell RCC', 'Hemangioblastoma', 'Pheochromocytoma'],
+            approvedDrugs: ['Belzutifan'],
+            mechanismOfAction: 'HIF-2α inhibition for VHL-deficient tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'VHL-altered tumors' },
+        { gene: 'TSC1/2', protein: 'Tuberous Sclerosis Complex', pathway: 'mTOR',
+            cancerTypes: ['Subependymal Giant Cell Astrocytoma', 'Angiomyolipoma', 'LAM'],
+            approvedDrugs: ['Everolimus'],
+            mechanismOfAction: 'mTOR inhibition for TSC-driven tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'TSC1/2 mutation' },
+        { gene: 'SMARCB1', protein: 'SWI/SNF Related BAF47', pathway: 'Chromatin Remodeling',
+            cancerTypes: ['Rhabdoid Tumor', 'Epithelioid Sarcoma', 'Malignant Rhabdoid Tumor'],
+            approvedDrugs: ['Tazemetostat'],
+            mechanismOfAction: 'EZH2 inhibition for INI1-deficient tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'SMARCB1/INI1 loss' },
+        { gene: 'FH', protein: 'Fumarate Hydratase', pathway: 'Metabolic',
+            cancerTypes: ['Hereditary Leiomyomatosis RCC', 'Uterine Leiomyoma'],
+            approvedDrugs: ['Bevacizumab + Erlotinib', 'Belzutifan (investigational)'],
+            mechanismOfAction: 'Target pseudohypoxia in FH-deficient tumors',
+            evidenceLevel: 'Phase II', biomarker: 'FH-deficient tumors' },
+        { gene: 'POLE/POLD1', protein: 'DNA Polymerase Epsilon/Delta', pathway: 'DNA Replication',
+            cancerTypes: ['Endometrial', 'Colorectal'],
+            approvedDrugs: ['Pembrolizumab', 'Checkpoint inhibitors'],
+            mechanismOfAction: 'Hypermutated tumors respond to immunotherapy',
+            evidenceLevel: 'FDA-Approved', biomarker: 'POLE ultramutated' },
+        // === RARE FUSION TARGETS ===
+        { gene: 'NRG1', protein: 'Neuregulin 1 Fusion', pathway: 'HER3/HER2',
+            cancerTypes: ['NSCLC', 'Pancreatic', 'Breast', 'Cholangiocarcinoma'],
+            approvedDrugs: ['Zenocutuzumab (investigational)', 'Afatinib'],
+            mechanismOfAction: 'Block NRG1 fusion-driven HER3 signaling',
+            evidenceLevel: 'Phase II', biomarker: 'NRG1 fusion' },
+        { gene: 'FGFR2 Fusion', protein: 'FGFR2 Fusion', pathway: 'FGFR',
+            cancerTypes: ['Cholangiocarcinoma', 'Bladder'],
+            approvedDrugs: ['Pemigatinib', 'Futibatinib', 'Infigratinib'],
+            mechanismOfAction: 'FGFR TKI for fusion-driven tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'FGFR2 fusion/rearrangement' },
+        { gene: 'RAF1 Fusion', protein: 'RAF1 Fusion', pathway: 'RAS/MAPK',
+            cancerTypes: ['Pilocytic Astrocytoma', 'Pancreatic', 'Prostate'],
+            approvedDrugs: ['Sorafenib', 'Pan-RAF inhibitors'],
+            mechanismOfAction: 'Inhibit RAF1 fusion kinase activity',
+            evidenceLevel: 'Phase II', biomarker: 'RAF1 fusion' },
+        // === IMMUNE MODULATORS ===
+        { gene: 'CD47', protein: 'CD47 "Don\'t Eat Me" Signal', pathway: 'Innate Immunity',
+            cancerTypes: ['AML', 'MDS', 'DLBCL', 'Solid Tumors'],
+            approvedDrugs: ['Magrolimab (investigational)', 'Lemzoparlimab (investigational)'],
+            mechanismOfAction: 'Block CD47-SIRPα to enable macrophage phagocytosis',
+            evidenceLevel: 'Phase III', biomarker: 'CD47+ malignancies' },
+        { gene: 'CD73', protein: 'Ecto-5\'-Nucleotidase', pathway: 'Adenosine Pathway',
+            cancerTypes: ['NSCLC', 'TNBC', 'Colorectal'],
+            approvedDrugs: ['Oleclumab (investigational)'],
+            mechanismOfAction: 'Block adenosine-mediated immunosuppression',
+            evidenceLevel: 'Phase II', biomarker: 'CD73 high tumors' },
+        { gene: 'TIM-3', protein: 'T-cell Immunoglobulin Mucin-3', pathway: 'Immune Checkpoint',
+            cancerTypes: ['AML', 'MDS', 'Solid Tumors'],
+            approvedDrugs: ['Sabatolimab (investigational)'],
+            mechanismOfAction: 'Block TIM-3 checkpoint receptor',
+            evidenceLevel: 'Phase II', biomarker: 'TIM-3 expression' },
+        { gene: 'ICOS', protein: 'Inducible T-cell Costimulator', pathway: 'Immune Costimulation',
+            cancerTypes: ['Solid Tumors', 'Lymphoma'],
+            approvedDrugs: ['ICOS agonists (investigational)'],
+            mechanismOfAction: 'Agonize ICOS to enhance T-cell activation',
+            evidenceLevel: 'Phase II', biomarker: 'ICOS+ T-cells in TME' },
+        { gene: 'OX40', protein: 'OX40 (CD134)', pathway: 'Immune Costimulation',
+            cancerTypes: ['Solid Tumors'],
+            approvedDrugs: ['OX40 agonists (investigational)'],
+            mechanismOfAction: 'Agonize OX40 to enhance effector T-cells',
+            evidenceLevel: 'Phase I', biomarker: 'T-cell infiltrated tumors' },
+        { gene: '4-1BB', protein: '4-1BB (CD137)', pathway: 'Immune Costimulation',
+            cancerTypes: ['Solid Tumors', 'Lymphoma'],
+            approvedDrugs: ['Utomilumab (investigational)'],
+            mechanismOfAction: 'Agonize 4-1BB to enhance T and NK cells',
+            evidenceLevel: 'Phase II', biomarker: '4-1BB+ immune cells' },
+        // === METABOLISM TARGETS ===
+        { gene: 'ASNS', protein: 'Asparagine Synthetase', pathway: 'Amino Acid Metabolism',
+            cancerTypes: ['ALL', 'AML', 'Solid Tumors'],
+            approvedDrugs: ['Asparaginase', 'Pegaspargase', 'Calaspargase pegol'],
+            mechanismOfAction: 'Deplete asparagine in ASNS-low tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'ASNS-low expression' },
+        { gene: 'DHODH', protein: 'Dihydroorotate Dehydrogenase', pathway: 'Pyrimidine Synthesis',
+            cancerTypes: ['AML', 'Solid Tumors'],
+            approvedDrugs: ['Brequinar (investigational)'],
+            mechanismOfAction: 'Block de novo pyrimidine synthesis',
+            evidenceLevel: 'Phase II', biomarker: 'DHODH-dependent tumors' },
+        { gene: 'MTAP', protein: 'Methylthioadenosine Phosphorylase', pathway: 'Methionine Salvage',
+            cancerTypes: ['Pancreatic', 'Glioblastoma', 'NSCLC', 'Mesothelioma'],
+            approvedDrugs: ['MAT2A inhibitors (investigational)', 'PRMT5 inhibitors (investigational)'],
+            mechanismOfAction: 'Synthetic lethality in MTAP-deleted tumors',
+            evidenceLevel: 'Phase II', biomarker: 'MTAP deletion (co-deleted with CDKN2A)' },
+        // === ALL KRAS VARIANTS ===
+        { gene: 'KRAS G12D', protein: 'KRAS G12D Mutant', pathway: 'RAS/MAPK',
+            cancerTypes: ['Pancreatic', 'Colorectal', 'NSCLC', 'Endometrial'],
+            approvedDrugs: ['MRTX1133 (investigational)', 'RMC-9805 (investigational)'],
+            mechanismOfAction: 'Direct KRAS G12D inhibition',
+            evidenceLevel: 'Phase I', biomarker: 'KRAS G12D mutation' },
+        { gene: 'KRAS G12V', protein: 'KRAS G12V Mutant', pathway: 'RAS/MAPK',
+            cancerTypes: ['Pancreatic', 'Colorectal', 'NSCLC'],
+            approvedDrugs: ['Pan-RAS inhibitors (investigational)', 'SOS1 inhibitors'],
+            mechanismOfAction: 'Indirect KRAS inhibition strategies',
+            evidenceLevel: 'Phase I', biomarker: 'KRAS G12V mutation' },
+        { gene: 'KRAS G13D', protein: 'KRAS G13D Mutant', pathway: 'RAS/MAPK',
+            cancerTypes: ['Colorectal', 'NSCLC'],
+            approvedDrugs: ['Cetuximab (may respond)', 'SHP2 inhibitors'],
+            mechanismOfAction: 'EGFR antibodies may work in G13D',
+            evidenceLevel: 'Phase II', biomarker: 'KRAS G13D mutation' },
+        { gene: 'KRAS G12R', protein: 'KRAS G12R Mutant', pathway: 'RAS/MAPK',
+            cancerTypes: ['Pancreatic'],
+            approvedDrugs: ['Pan-RAS inhibitors (investigational)'],
+            mechanismOfAction: 'Novel RAS inhibition approaches',
+            evidenceLevel: 'Phase I', biomarker: 'KRAS G12R mutation' },
+        { gene: 'KRAS Q61H/L/K', protein: 'KRAS Q61 Mutants', pathway: 'RAS/MAPK',
+            cancerTypes: ['Melanoma', 'NSCLC', 'Colorectal'],
+            approvedDrugs: ['MEK inhibitors', 'ERK inhibitors (investigational)'],
+            mechanismOfAction: 'Downstream pathway inhibition',
+            evidenceLevel: 'Phase II', biomarker: 'KRAS Q61 mutations' },
+        { gene: 'NRAS Q61', protein: 'NRAS Q61 Mutant', pathway: 'RAS/MAPK',
+            cancerTypes: ['Melanoma', 'AML', 'Colorectal'],
+            approvedDrugs: ['Binimetinib', 'MEK inhibitors'],
+            mechanismOfAction: 'MEK inhibition for NRAS-mutant tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'NRAS mutation' },
+        { gene: 'HRAS', protein: 'HRAS Mutant', pathway: 'RAS/MAPK',
+            cancerTypes: ['Head and Neck', 'Bladder', 'Thyroid'],
+            approvedDrugs: ['Tipifarnib'],
+            mechanismOfAction: 'Farnesyltransferase inhibition',
+            evidenceLevel: 'FDA-Approved', biomarker: 'HRAS mutation' },
+        // === HEREDITARY CANCER SYNDROME TARGETS ===
+        { gene: 'MLH1/MSH2/MSH6/PMS2', protein: 'Mismatch Repair Proteins', pathway: 'DNA Repair',
+            cancerTypes: ['Lynch Syndrome Cancers', 'Colorectal', 'Endometrial', 'Ovarian', 'Gastric'],
+            approvedDrugs: ['Pembrolizumab', 'Nivolumab', 'Dostarlimab'],
+            mechanismOfAction: 'Immunotherapy for dMMR tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'dMMR/MSI-H (Lynch syndrome)' },
+        { gene: 'TP53 (Li-Fraumeni)', protein: 'p53 Tumor Suppressor', pathway: 'Cell Cycle/Apoptosis',
+            cancerTypes: ['Li-Fraumeni Syndrome', 'Sarcoma', 'Breast', 'Brain', 'Adrenocortical'],
+            approvedDrugs: ['Intensive surveillance', 'MDM2 inhibitors (investigational)', 'Gene therapy (investigational)'],
+            mechanismOfAction: 'Restore p53 function or surveillance',
+            evidenceLevel: 'Phase II', biomarker: 'Germline TP53 mutation' },
+        { gene: 'APC', protein: 'Adenomatous Polyposis Coli', pathway: 'Wnt/β-catenin',
+            cancerTypes: ['FAP Colorectal', 'Desmoid Tumor'],
+            approvedDrugs: ['Sulindac', 'Celecoxib', 'Nirogacestat (desmoid)'],
+            mechanismOfAction: 'COX inhibition, Notch inhibition',
+            evidenceLevel: 'FDA-Approved', biomarker: 'APC mutation (FAP)' },
+        { gene: 'STK11/LKB1', protein: 'Serine/Threonine Kinase 11', pathway: 'AMPK/mTOR',
+            cancerTypes: ['Peutz-Jeghers Syndrome', 'NSCLC', 'Cervical'],
+            approvedDrugs: ['mTOR inhibitors', 'Chemotherapy (reduced ICI response)'],
+            mechanismOfAction: 'Target downstream pathways',
+            evidenceLevel: 'Phase II', biomarker: 'STK11/LKB1 loss' },
+        { gene: 'PTEN (Cowden)', protein: 'PTEN Tumor Suppressor', pathway: 'PI3K/AKT',
+            cancerTypes: ['Cowden Syndrome', 'Breast', 'Thyroid', 'Endometrial'],
+            approvedDrugs: ['PI3K inhibitors', 'AKT inhibitors', 'mTOR inhibitors'],
+            mechanismOfAction: 'Inhibit hyperactive PI3K pathway',
+            evidenceLevel: 'FDA-Approved', biomarker: 'PTEN loss (Cowden syndrome)' },
+        { gene: 'CDH1', protein: 'E-cadherin', pathway: 'Cell Adhesion',
+            cancerTypes: ['Hereditary Diffuse Gastric Cancer', 'Lobular Breast'],
+            approvedDrugs: ['Prophylactic gastrectomy', 'Surveillance', 'Standard chemo'],
+            mechanismOfAction: 'Surgical prevention or standard treatment',
+            evidenceLevel: 'FDA-Approved', biomarker: 'CDH1 germline mutation' },
+        { gene: 'CHEK2', protein: 'Checkpoint Kinase 2', pathway: 'DNA Damage Response',
+            cancerTypes: ['Breast', 'Colorectal', 'Prostate'],
+            approvedDrugs: ['PARP inhibitors (investigational)', 'ATR inhibitors'],
+            mechanismOfAction: 'Exploit DNA repair deficiency',
+            evidenceLevel: 'Phase II', biomarker: 'CHEK2 mutation' },
+        { gene: 'PALB2', protein: 'Partner and Localizer of BRCA2', pathway: 'Homologous Recombination',
+            cancerTypes: ['Breast', 'Pancreatic', 'Ovarian'],
+            approvedDrugs: ['Olaparib', 'Rucaparib', 'Platinum chemotherapy'],
+            mechanismOfAction: 'PARP inhibition for HRD',
+            evidenceLevel: 'FDA-Approved', biomarker: 'PALB2 mutation' },
+        { gene: 'RAD51C/D', protein: 'RAD51 Paralogs', pathway: 'Homologous Recombination',
+            cancerTypes: ['Ovarian', 'Breast'],
+            approvedDrugs: ['PARP inhibitors', 'Platinum'],
+            mechanismOfAction: 'Synthetic lethality in HRD',
+            evidenceLevel: 'FDA-Approved', biomarker: 'RAD51C/D mutation' },
+        { gene: 'BAP1', protein: 'BRCA1-Associated Protein 1', pathway: 'Chromatin/DNA Repair',
+            cancerTypes: ['Mesothelioma', 'Uveal Melanoma', 'RCC', 'Cholangiocarcinoma'],
+            approvedDrugs: ['EZH2 inhibitors (investigational)', 'PARP inhibitors', 'Immunotherapy'],
+            mechanismOfAction: 'Exploit epigenetic vulnerability',
+            evidenceLevel: 'Phase II', biomarker: 'BAP1 loss/mutation' },
+        { gene: 'MEN1', protein: 'Menin', pathway: 'Transcription Regulation',
+            cancerTypes: ['MEN1 Syndrome', 'Pancreatic NET', 'Pituitary', 'Parathyroid'],
+            approvedDrugs: ['Somatostatin analogues', 'Everolimus', 'Sunitinib'],
+            mechanismOfAction: 'Manage neuroendocrine tumors',
+            evidenceLevel: 'FDA-Approved', biomarker: 'MEN1 germline mutation' },
+        { gene: 'RB1', protein: 'Retinoblastoma Protein', pathway: 'Cell Cycle',
+            cancerTypes: ['Retinoblastoma', 'Osteosarcoma', 'SCLC'],
+            approvedDrugs: ['CDK4/6 inhibitors (if RB intact)', 'Chemotherapy', 'Focal therapy'],
+            mechanismOfAction: 'Target cell cycle or standard therapy',
+            evidenceLevel: 'FDA-Approved', biomarker: 'RB1 mutation/loss' },
+        // === HIV/IMMUNOCOMPROMISED CANCER TARGETS ===
+        { gene: 'HHV8/KSHV', protein: 'Kaposi Sarcoma Herpesvirus', pathway: 'Viral Oncogenesis',
+            cancerTypes: ['Kaposi Sarcoma', 'Primary Effusion Lymphoma', 'Multicentric Castleman'],
+            approvedDrugs: ['ART', 'Liposomal Doxorubicin', 'Paclitaxel', 'Pomalidomide', 'Siltuximab'],
+            mechanismOfAction: 'Immune reconstitution + direct therapy',
+            evidenceLevel: 'FDA-Approved', biomarker: 'HHV8+ malignancy' },
+        { gene: 'EBV', protein: 'Epstein-Barr Virus', pathway: 'Viral Oncogenesis',
+            cancerTypes: ['PTLD', 'Nasopharyngeal', 'Burkitt Lymphoma', 'Hodgkin', 'Gastric'],
+            approvedDrugs: ['Rituximab (PTLD)', 'EBV-specific CTLs', 'Tabelecleucel', 'Chemotherapy'],
+            mechanismOfAction: 'Target EBV+ cells or reduce immunosuppression',
+            evidenceLevel: 'FDA-Approved', biomarker: 'EBV+ malignancy' },
+        { gene: 'HPV', protein: 'Human Papillomavirus', pathway: 'Viral Oncogenesis',
+            cancerTypes: ['Cervical', 'OPSCC', 'Anal', 'Vulvar', 'Vaginal', 'Penile'],
+            approvedDrugs: ['Tisotumab Vedotin', 'Pembrolizumab', 'Chemoradiation'],
+            mechanismOfAction: 'Target HPV-driven cancers',
+            evidenceLevel: 'FDA-Approved', biomarker: 'HPV+ cancer' },
+        { gene: 'HBV/HCV', protein: 'Hepatitis B/C Viruses', pathway: 'Viral Oncogenesis',
+            cancerTypes: ['HCC'],
+            approvedDrugs: ['Antiviral therapy', 'Atezolizumab-Bevacizumab', 'Sorafenib', 'Lenvatinib'],
+            mechanismOfAction: 'Viral suppression + HCC treatment',
+            evidenceLevel: 'FDA-Approved', biomarker: 'HBV/HCV-related HCC' },
+        // === CNS-PENETRANT THERAPY TARGETS ===
+        { gene: 'CNS-EGFR', protein: 'CNS-Penetrant EGFR Inhibition', pathway: 'EGFR',
+            cancerTypes: ['NSCLC Brain Mets', 'EGFR+ with LMD'],
+            approvedDrugs: ['Osimertinib (CNS-penetrant)', 'High-dose Gefitinib'],
+            mechanismOfAction: 'Cross blood-brain barrier',
+            evidenceLevel: 'FDA-Approved', biomarker: 'EGFR+ NSCLC with CNS disease' },
+        { gene: 'CNS-ALK', protein: 'CNS-Penetrant ALK Inhibition', pathway: 'ALK',
+            cancerTypes: ['ALK+ NSCLC Brain Mets'],
+            approvedDrugs: ['Lorlatinib', 'Alectinib', 'Brigatinib'],
+            mechanismOfAction: 'High CNS penetration',
+            evidenceLevel: 'FDA-Approved', biomarker: 'ALK+ NSCLC with CNS disease' },
+        { gene: 'CNS-HER2', protein: 'CNS-Penetrant HER2 Therapy', pathway: 'HER2',
+            cancerTypes: ['HER2+ Breast Brain Mets'],
+            approvedDrugs: ['Tucatinib + Trastuzumab', 'T-DXd', 'Lapatinib'],
+            mechanismOfAction: 'CNS-penetrant HER2 inhibition',
+            evidenceLevel: 'FDA-Approved', biomarker: 'HER2+ breast with CNS disease' },
+        { gene: 'CNS-Melanoma', protein: 'CNS-Active Melanoma Therapy', pathway: 'Multiple',
+            cancerTypes: ['Melanoma Brain Mets'],
+            approvedDrugs: ['Nivolumab + Ipilimumab', 'BRAF/MEK (if BRAF+)', 'SRS'],
+            mechanismOfAction: 'Immunotherapy reaches CNS',
+            evidenceLevel: 'FDA-Approved', biomarker: 'Melanoma with CNS disease' },
+        // === RESISTANCE MECHANISM TARGETS ===
+        { gene: 'EGFR C797S', protein: 'EGFR C797S Resistance', pathway: 'EGFR',
+            cancerTypes: ['NSCLC post-Osimertinib'],
+            approvedDrugs: ['Amivantamab', 'Chemotherapy', 'EGFR-MET bispecifics', '4th-gen TKIs (investigational)'],
+            mechanismOfAction: 'Overcome covalent TKI resistance',
+            evidenceLevel: 'FDA-Approved', biomarker: 'EGFR C797S after osimertinib' },
+        { gene: 'ALK Resistance', protein: 'ALK Compound Mutations', pathway: 'ALK',
+            cancerTypes: ['ALK+ NSCLC resistant'],
+            approvedDrugs: ['Lorlatinib', 'Sequential ALK TKIs based on mutation'],
+            mechanismOfAction: 'Select TKI by resistance profile',
+            evidenceLevel: 'FDA-Approved', biomarker: 'ALK resistance mutations' },
+        { gene: 'ESR1 Mutations', protein: 'Estrogen Receptor Mutations', pathway: 'Hormone',
+            cancerTypes: ['HR+ Breast post-AI'],
+            approvedDrugs: ['Elacestrant', 'Fulvestrant', 'Novel SERDs'],
+            mechanismOfAction: 'SERD for ESR1-mutant breast cancer',
+            evidenceLevel: 'FDA-Approved', biomarker: 'ESR1 mutation' },
+        { gene: 'AR Splice Variants', protein: 'AR-V7', pathway: 'Hormone',
+            cancerTypes: ['mCRPC'],
+            approvedDrugs: ['Taxanes preferred', 'PSMA radioligand', 'Consider avoiding AR-targeted'],
+            mechanismOfAction: 'AR-V7+ predicts AR therapy resistance',
+            evidenceLevel: 'FDA-Approved', biomarker: 'AR-V7 positive' },
+        { gene: 'BTK C481S', protein: 'BTK Covalent Resistance', pathway: 'BCR Signaling',
+            cancerTypes: ['CLL/MCL post-Ibrutinib'],
+            approvedDrugs: ['Pirtobrutinib', 'Venetoclax', 'Non-covalent BTK inhibitors'],
+            mechanismOfAction: 'Non-covalent BTK inhibition',
+            evidenceLevel: 'FDA-Approved', biomarker: 'BTK C481S mutation' },
+        { gene: 'BCR-ABL T315I', protein: 'BCR-ABL Gatekeeper Mutation', pathway: 'BCR-ABL',
+            cancerTypes: ['CML', 'Ph+ ALL'],
+            approvedDrugs: ['Ponatinib', 'Asciminib'],
+            mechanismOfAction: 'Overcome T315I resistance',
+            evidenceLevel: 'FDA-Approved', biomarker: 'BCR-ABL T315I' },
+        { gene: 'MET Amplification', protein: 'MET Bypass Resistance', pathway: 'MET',
+            cancerTypes: ['EGFR+ NSCLC resistant'],
+            approvedDrugs: ['Amivantamab + Lazertinib', 'Capmatinib + Osimertinib', 'Tepotinib'],
+            mechanismOfAction: 'Dual EGFR/MET inhibition',
+            evidenceLevel: 'FDA-Approved', biomarker: 'MET amplification as resistance' },
+        // === OLIGOMETASTATIC DISEASE TARGETS ===
+        { gene: 'Oligomet', protein: 'Oligometastatic Disease', pathway: 'Multiple',
+            cancerTypes: ['NSCLC Oligomet', 'Colorectal Liver Mets', 'Prostate Oligomet'],
+            approvedDrugs: ['SBRT', 'Metastasectomy', 'Local ablation', 'Continued systemic'],
+            mechanismOfAction: 'Consolidative local therapy',
+            evidenceLevel: 'FDA-Approved', biomarker: 'Limited metastatic burden (1-5 mets)' },
+        // === THERAPY-RELATED MALIGNANCY TARGETS ===
+        { gene: 't-MN', protein: 'Therapy-Related Myeloid Neoplasm', pathway: 'Multiple',
+            cancerTypes: ['t-AML', 't-MDS'],
+            approvedDrugs: ['CPX-351 (favorable)', 'Venetoclax-HMA', 'Allogeneic transplant'],
+            mechanismOfAction: 'Intensive therapy if fit, otherwise HMA-based',
+            evidenceLevel: 'FDA-Approved', biomarker: 'Prior chemo/radiation exposure' },
+        // === SPECIAL POPULATIONS ===
+        { gene: 'Organ Transplant', protein: 'Post-Transplant Malignancy', pathway: 'Multiple',
+            cancerTypes: ['PTLD', 'Skin Cancer', 'Kaposi', 'Any post-transplant'],
+            approvedDrugs: ['Reduce immunosuppression', 'Rituximab (PTLD)', 'mTOR-based IS'],
+            mechanismOfAction: 'Balance rejection risk vs cancer treatment',
+            evidenceLevel: 'FDA-Approved', biomarker: 'Solid organ transplant recipient' },
+        { gene: 'Autoimmune', protein: 'Cancer with Autoimmune Disease', pathway: 'Immune',
+            cancerTypes: ['Any cancer with autoimmune comorbidity'],
+            approvedDrugs: ['Checkpoint inhibitors with caution', 'Targeted therapy preferred', 'Close monitoring'],
+            mechanismOfAction: 'Risk-benefit assessment for immunotherapy',
+            evidenceLevel: 'FDA-Approved', biomarker: 'Pre-existing autoimmune disease' }
     ];
     // ═══════════════════════════════════════════════════════════════════════════════
     // IMMUNOTHERAPY PROTOCOLS
@@ -312,7 +723,129 @@ export class CancerTreatmentCapabilityModule {
             targets: ['Tumor Neoantigens'], drugs: ['Lifileucel'],
             cancerTypes: ['Melanoma'],
             responseRate: 0.36, durableResponseRate: 0.22,
-            biomarkers: ['Unresectable/metastatic melanoma'] }
+            biomarkers: ['Unresectable/metastatic melanoma'] },
+        // === ADDITIONAL CHECKPOINT INHIBITOR COMBINATIONS ===
+        { id: 'ici-durva-treme', name: 'Durvalumab + Tremelimumab', type: 'checkpoint_inhibitor',
+            targets: ['PD-L1', 'CTLA-4'], drugs: ['Durvalumab', 'Tremelimumab'],
+            cancerTypes: ['HCC', 'NSCLC', 'Bladder'],
+            responseRate: 0.45, durableResponseRate: 0.30,
+            biomarkers: ['PD-L1 expression'] },
+        { id: 'ici-atezo-bev', name: 'Atezolizumab + Bevacizumab', type: 'checkpoint_inhibitor',
+            targets: ['PD-L1', 'VEGF'], drugs: ['Atezolizumab', 'Bevacizumab'],
+            cancerTypes: ['HCC', 'RCC'],
+            responseRate: 0.52, durableResponseRate: 0.35,
+            biomarkers: ['Child-Pugh A liver function'] },
+        { id: 'ici-pembro-lenva', name: 'Pembrolizumab + Lenvatinib', type: 'checkpoint_inhibitor',
+            targets: ['PD-1', 'VEGFR/FGFR'], drugs: ['Pembrolizumab', 'Lenvatinib'],
+            cancerTypes: ['Endometrial', 'RCC', 'HCC'],
+            responseRate: 0.48, durableResponseRate: 0.32,
+            biomarkers: ['Non-MSI-H, dMMR endometrial'] },
+        { id: 'ici-nivo-cabo', name: 'Nivolumab + Cabozantinib', type: 'checkpoint_inhibitor',
+            targets: ['PD-1', 'VEGFR/MET/AXL'], drugs: ['Nivolumab', 'Cabozantinib'],
+            cancerTypes: ['RCC'],
+            responseRate: 0.55, durableResponseRate: 0.38,
+            biomarkers: ['Advanced RCC'] },
+        // === CAR-T FOR ADDITIONAL TARGETS ===
+        { id: 'car-t-cd22', name: 'CD22-directed CAR-T Therapy', type: 'car_t',
+            targets: ['CD22'], drugs: ['Investigational CD22 CAR-T'],
+            cancerTypes: ['B-ALL (CD19-relapsed)', 'DLBCL'],
+            responseRate: 0.70, durableResponseRate: 0.35,
+            biomarkers: ['CD22+ B-cell malignancy', 'CD19 CAR-T failure'] },
+        { id: 'car-t-cd7', name: 'CD7-directed CAR-T Therapy', type: 'car_t',
+            targets: ['CD7'], drugs: ['Investigational CD7 CAR-T'],
+            cancerTypes: ['T-ALL', 'T-cell Lymphoma'],
+            responseRate: 0.65, durableResponseRate: 0.28,
+            biomarkers: ['CD7+ T-cell malignancy'] },
+        { id: 'car-t-gpc3', name: 'GPC3-directed CAR-T Therapy', type: 'car_t',
+            targets: ['GPC3'], drugs: ['Investigational GPC3 CAR-T'],
+            cancerTypes: ['HCC', 'Hepatoblastoma'],
+            responseRate: 0.45, durableResponseRate: 0.18,
+            biomarkers: ['GPC3+ liver cancer'] },
+        { id: 'car-t-mesothelin', name: 'Mesothelin-directed CAR-T Therapy', type: 'car_t',
+            targets: ['Mesothelin'], drugs: ['Investigational Mesothelin CAR-T'],
+            cancerTypes: ['Mesothelioma', 'Pancreatic', 'Ovarian'],
+            responseRate: 0.35, durableResponseRate: 0.12,
+            biomarkers: ['Mesothelin+ solid tumors'] },
+        { id: 'car-t-gd2', name: 'GD2-directed CAR-T Therapy', type: 'car_t',
+            targets: ['GD2'], drugs: ['Investigational GD2 CAR-T'],
+            cancerTypes: ['Neuroblastoma', 'Osteosarcoma', 'Melanoma'],
+            responseRate: 0.50, durableResponseRate: 0.25,
+            biomarkers: ['GD2+ pediatric solid tumors'] },
+        { id: 'car-t-claudin18', name: 'Claudin 18.2-directed CAR-T Therapy', type: 'car_t',
+            targets: ['Claudin 18.2'], drugs: ['CT041 (investigational)'],
+            cancerTypes: ['Gastric', 'Pancreatic', 'GE Junction'],
+            responseRate: 0.55, durableResponseRate: 0.22,
+            biomarkers: ['Claudin 18.2+ GI cancers'] },
+        // === NK CELL THERAPIES ===
+        { id: 'nk-cell-therapy', name: 'Allogeneic NK Cell Therapy', type: 'cytokine_therapy',
+            targets: ['Tumor Cells'], drugs: ['FT516', 'FT596'],
+            cancerTypes: ['AML', 'Lymphoma', 'Solid Tumors'],
+            responseRate: 0.45, durableResponseRate: 0.20,
+            biomarkers: ['Relapsed/Refractory malignancy'] },
+        { id: 'nk-car-therapy', name: 'CAR-NK Cell Therapy', type: 'car_t',
+            targets: ['CD19', 'HER2', 'GD2'], drugs: ['Off-the-shelf CAR-NK'],
+            cancerTypes: ['B-cell Lymphoma', 'Solid Tumors'],
+            responseRate: 0.50, durableResponseRate: 0.22,
+            biomarkers: ['Target antigen positive'] },
+        // === BISPECIFIC ANTIBODY THERAPIES ===
+        { id: 'bispec-teclistamab', name: 'Teclistamab (BCMAxCD3)', type: 'checkpoint_inhibitor',
+            targets: ['BCMA', 'CD3'], drugs: ['Teclistamab'],
+            cancerTypes: ['Multiple Myeloma'],
+            responseRate: 0.63, durableResponseRate: 0.35,
+            biomarkers: ['Relapsed/Refractory MM'] },
+        { id: 'bispec-mosunetuzumab', name: 'Mosunetuzumab (CD20xCD3)', type: 'checkpoint_inhibitor',
+            targets: ['CD20', 'CD3'], drugs: ['Mosunetuzumab'],
+            cancerTypes: ['Follicular Lymphoma', 'DLBCL'],
+            responseRate: 0.80, durableResponseRate: 0.45,
+            biomarkers: ['CD20+ B-cell lymphoma'] },
+        { id: 'bispec-glofitamab', name: 'Glofitamab (CD20xCD3)', type: 'checkpoint_inhibitor',
+            targets: ['CD20', 'CD3'], drugs: ['Glofitamab'],
+            cancerTypes: ['DLBCL', 'Aggressive B-cell Lymphoma'],
+            responseRate: 0.52, durableResponseRate: 0.30,
+            biomarkers: ['CD20+ aggressive lymphoma'] },
+        { id: 'bispec-tarlatamab', name: 'Tarlatamab (DLL3xCD3)', type: 'checkpoint_inhibitor',
+            targets: ['DLL3', 'CD3'], drugs: ['Tarlatamab'],
+            cancerTypes: ['SCLC', 'Large Cell Neuroendocrine'],
+            responseRate: 0.40, durableResponseRate: 0.22,
+            biomarkers: ['DLL3+ neuroendocrine tumors'] },
+        { id: 'bispec-talquetamab', name: 'Talquetamab (GPRC5DxCD3)', type: 'checkpoint_inhibitor',
+            targets: ['GPRC5D', 'CD3'], drugs: ['Talquetamab'],
+            cancerTypes: ['Multiple Myeloma'],
+            responseRate: 0.70, durableResponseRate: 0.32,
+            biomarkers: ['GPRC5D+ myeloma'] },
+        // === ONCOLYTIC VIRUS THERAPY ===
+        { id: 'ov-tvec', name: 'Talimogene Laherparepvec (T-VEC)', type: 'oncolytic_virus',
+            targets: ['Tumor Cells'], drugs: ['Talimogene laherparepvec'],
+            cancerTypes: ['Melanoma'],
+            responseRate: 0.26, durableResponseRate: 0.16,
+            biomarkers: ['Injectable melanoma lesions'] },
+        { id: 'ov-delytact', name: 'Delytact (Teserpaturev)', type: 'oncolytic_virus',
+            targets: ['Tumor Cells'], drugs: ['Teserpaturev'],
+            cancerTypes: ['Glioblastoma'],
+            responseRate: 0.30, durableResponseRate: 0.15,
+            biomarkers: ['Recurrent glioblastoma'] },
+        // === CANCER VACCINES ===
+        { id: 'vaccine-sipuleucel', name: 'Sipuleucel-T (Provenge)', type: 'cancer_vaccine',
+            targets: ['PAP'], drugs: ['Sipuleucel-T'],
+            cancerTypes: ['Prostate'],
+            responseRate: 0.20, durableResponseRate: 0.15,
+            biomarkers: ['Asymptomatic/minimally symptomatic mCRPC'] },
+        { id: 'vaccine-neoantigen', name: 'Personalized Neoantigen Vaccine', type: 'cancer_vaccine',
+            targets: ['Patient-Specific Neoantigens'], drugs: ['mRNA-4157', 'Autogene Cevumeran'],
+            cancerTypes: ['Melanoma', 'NSCLC', 'Pancreatic', 'Colorectal'],
+            responseRate: 0.35, durableResponseRate: 0.25,
+            biomarkers: ['High TMB', 'MSI-H'] },
+        // === CYTOKINE THERAPIES ===
+        { id: 'cytokine-il2', name: 'High-Dose IL-2', type: 'cytokine_therapy',
+            targets: ['T-cells', 'NK cells'], drugs: ['Aldesleukin'],
+            cancerTypes: ['Melanoma', 'RCC'],
+            responseRate: 0.15, durableResponseRate: 0.10,
+            biomarkers: ['Good performance status'] },
+        { id: 'cytokine-pegifn', name: 'Pegylated Interferon Alpha', type: 'cytokine_therapy',
+            targets: ['Immune System'], drugs: ['Peginterferon alfa-2b'],
+            cancerTypes: ['Melanoma (adjuvant)', 'MPN'],
+            responseRate: 0.25, durableResponseRate: 0.18,
+            biomarkers: ['Stage III melanoma'] }
     ];
     // ═══════════════════════════════════════════════════════════════════════════════
     // COMBINATION THERAPIES
@@ -345,7 +878,128 @@ export class CancerTreatmentCapabilityModule {
         { id: 'combo-bcl2-aza', name: 'BCL-2 + Hypomethylating Agent',
             components: ['Venetoclax', 'Azacitidine'],
             synergisticEffect: 1.6, cancerTypes: ['AML'],
-            clinicalEvidence: 'VIALE-A: 64.7% CR+CRi rate' }
+            clinicalEvidence: 'VIALE-A: 64.7% CR+CRi rate' },
+        // === ADDITIONAL COMBINATIONS FOR COMPREHENSIVE COVERAGE ===
+        { id: 'combo-trastuzumab-deruxtecan', name: 'T-DXd for HER2-Low',
+            components: ['Trastuzumab Deruxtecan'],
+            synergisticEffect: 1.5, cancerTypes: ['HER2-Low Breast', 'Gastric', 'NSCLC'],
+            clinicalEvidence: 'DESTINY-Breast04: 9.9mo PFS in HER2-low' },
+        { id: 'combo-enfortumab-pembro', name: 'Enfortumab + Pembrolizumab',
+            components: ['Enfortumab Vedotin', 'Pembrolizumab'],
+            synergisticEffect: 1.55, cancerTypes: ['Bladder', 'Urothelial'],
+            clinicalEvidence: 'EV-302: 31.5mo OS vs 16.1mo chemo' },
+        { id: 'combo-sacituzumab-tnbc', name: 'Sacituzumab Govitecan for TNBC',
+            components: ['Sacituzumab Govitecan'],
+            synergisticEffect: 1.4, cancerTypes: ['TNBC', 'Bladder'],
+            clinicalEvidence: 'ASCENT: 12.1mo OS in metastatic TNBC' },
+        { id: 'combo-folfox-bev', name: 'FOLFOX + Bevacizumab',
+            components: ['5-FU', 'Leucovorin', 'Oxaliplatin', 'Bevacizumab'],
+            synergisticEffect: 1.3, cancerTypes: ['Colorectal'],
+            clinicalEvidence: 'Standard 1L mCRC backbone' },
+        { id: 'combo-folfiri-cetux', name: 'FOLFIRI + Cetuximab (RAS WT)',
+            components: ['5-FU', 'Leucovorin', 'Irinotecan', 'Cetuximab'],
+            synergisticEffect: 1.35, cancerTypes: ['Colorectal (RAS WT)'],
+            clinicalEvidence: 'FIRE-3: Improved OS in left-sided mCRC' },
+        { id: 'combo-gem-nab-pac', name: 'Gemcitabine + nab-Paclitaxel',
+            components: ['Gemcitabine', 'nab-Paclitaxel'],
+            synergisticEffect: 1.25, cancerTypes: ['Pancreatic'],
+            clinicalEvidence: 'MPACT: 8.5mo OS in metastatic PDAC' },
+        { id: 'combo-folfirinox', name: 'FOLFIRINOX',
+            components: ['5-FU', 'Leucovorin', 'Irinotecan', 'Oxaliplatin'],
+            synergisticEffect: 1.4, cancerTypes: ['Pancreatic'],
+            clinicalEvidence: 'PRODIGE 4: 11.1mo OS in fit patients' },
+        { id: 'combo-osimertinib-chemo', name: 'Osimertinib + Chemotherapy',
+            components: ['Osimertinib', 'Carboplatin', 'Pemetrexed'],
+            synergisticEffect: 1.35, cancerTypes: ['EGFR+ NSCLC'],
+            clinicalEvidence: 'FLAURA2: 25.5mo PFS' },
+        { id: 'combo-cabo-atezo', name: 'Cabozantinib + Atezolizumab',
+            components: ['Cabozantinib', 'Atezolizumab'],
+            synergisticEffect: 1.4, cancerTypes: ['RCC', 'HCC'],
+            clinicalEvidence: 'COSMIC-311: Improved PFS in thyroid cancer' },
+        { id: 'combo-btk-venetoclax', name: 'BTK Inhibitor + Venetoclax',
+            components: ['Ibrutinib', 'Venetoclax'],
+            synergisticEffect: 1.65, cancerTypes: ['CLL', 'Mantle Cell'],
+            clinicalEvidence: 'CAPTIVATE: 88% uMRD rates' },
+        { id: 'combo-daratumumab-vrd', name: 'Daratumumab-VRd',
+            components: ['Daratumumab', 'Bortezomib', 'Lenalidomide', 'Dexamethasone'],
+            synergisticEffect: 1.5, cancerTypes: ['Multiple Myeloma'],
+            clinicalEvidence: 'PERSEUS: 84% sCR rate in newly diagnosed' },
+        { id: 'combo-tki-mek', name: 'TKI + MEK Inhibitor',
+            components: ['Various TKIs', 'MEK inhibitors'],
+            synergisticEffect: 1.35, cancerTypes: ['KRAS mutant tumors'],
+            clinicalEvidence: 'Combination to overcome resistance' },
+        { id: 'combo-adc-ici', name: 'ADC + Checkpoint Inhibitor',
+            components: ['Various ADCs', 'Pembrolizumab'],
+            synergisticEffect: 1.4, cancerTypes: ['Solid Tumors'],
+            clinicalEvidence: 'Emerging data showing enhanced efficacy' },
+        { id: 'combo-prrt-177lu', name: 'PRRT with 177Lu-DOTATATE',
+            components: ['177Lu-DOTATATE', 'Octreotide LAR'],
+            synergisticEffect: 1.45, cancerTypes: ['GI NET', 'Pancreatic NET'],
+            clinicalEvidence: 'NETTER-1: 79% reduction in progression' },
+        { id: 'combo-psma-rlt', name: 'PSMA Radioligand Therapy',
+            components: ['177Lu-PSMA-617', 'Standard of Care'],
+            synergisticEffect: 1.5, cancerTypes: ['mCRPC'],
+            clinicalEvidence: 'VISION: 4mo OS improvement' },
+        { id: 'combo-intensive-chemo-all', name: 'Intensive ALL Induction',
+            components: ['Vincristine', 'Prednisone', 'Daunorubicin', 'Asparaginase'],
+            synergisticEffect: 1.55, cancerTypes: ['ALL', 'Pediatric ALL'],
+            clinicalEvidence: '90%+ CR rates in pediatric ALL' },
+        { id: 'combo-r-chop', name: 'R-CHOP',
+            components: ['Rituximab', 'Cyclophosphamide', 'Doxorubicin', 'Vincristine', 'Prednisone'],
+            synergisticEffect: 1.5, cancerTypes: ['DLBCL', 'Follicular Lymphoma'],
+            clinicalEvidence: 'Standard of care for aggressive B-cell lymphoma' },
+        { id: 'combo-abvd', name: 'ABVD for Hodgkin',
+            components: ['Doxorubicin', 'Bleomycin', 'Vinblastine', 'Dacarbazine'],
+            synergisticEffect: 1.45, cancerTypes: ['Hodgkin Lymphoma'],
+            clinicalEvidence: '80%+ cure rate in early-stage HL' },
+        { id: 'combo-bv-avd', name: 'Brentuximab-AVD',
+            components: ['Brentuximab Vedotin', 'Doxorubicin', 'Vinblastine', 'Dacarbazine'],
+            synergisticEffect: 1.55, cancerTypes: ['Hodgkin Lymphoma (Advanced)'],
+            clinicalEvidence: 'ECHELON-1: Improved PFS over ABVD' },
+        { id: 'combo-carbo-taxol-bev', name: 'Carboplatin/Paclitaxel/Bevacizumab',
+            components: ['Carboplatin', 'Paclitaxel', 'Bevacizumab'],
+            synergisticEffect: 1.35, cancerTypes: ['Ovarian', 'NSCLC', 'Cervical'],
+            clinicalEvidence: 'GOG-0218: Improved PFS in ovarian' },
+        { id: 'combo-parp-bev', name: 'PARP + Bevacizumab Maintenance',
+            components: ['Olaparib', 'Bevacizumab'],
+            synergisticEffect: 1.5, cancerTypes: ['Ovarian (HRD+)'],
+            clinicalEvidence: 'PAOLA-1: 37.2mo PFS in HRD+ ovarian' },
+        { id: 'combo-temozolomide-rt', name: 'Temozolomide + Radiation (Stupp)',
+            components: ['Temozolomide', 'Radiation'],
+            synergisticEffect: 1.4, cancerTypes: ['Glioblastoma'],
+            clinicalEvidence: 'Stupp protocol: Standard of care GBM' },
+        { id: 'combo-ttfields-tmz', name: 'TTFields + Temozolomide',
+            components: ['Tumor Treating Fields', 'Temozolomide'],
+            synergisticEffect: 1.3, cancerTypes: ['Glioblastoma'],
+            clinicalEvidence: 'EF-14: Improved OS in newly diagnosed GBM' },
+        { id: 'combo-cisplatin-rt-hnscc', name: 'Cisplatin + Radiation (HNSCC)',
+            components: ['Cisplatin', 'Radiation'],
+            synergisticEffect: 1.4, cancerTypes: ['HNSCC', 'Nasopharyngeal'],
+            clinicalEvidence: 'Standard concurrent chemoradiation' },
+        { id: 'combo-pembro-chemo-hnscc', name: 'Pembrolizumab + Chemo (HNSCC)',
+            components: ['Pembrolizumab', 'Platinum', '5-FU'],
+            synergisticEffect: 1.45, cancerTypes: ['HNSCC (1L)'],
+            clinicalEvidence: 'KEYNOTE-048: Improved OS' },
+        { id: 'combo-gem-cis-cholang', name: 'Gemcitabine/Cisplatin + Durvalumab',
+            components: ['Gemcitabine', 'Cisplatin', 'Durvalumab'],
+            synergisticEffect: 1.4, cancerTypes: ['Cholangiocarcinoma', 'Biliary'],
+            clinicalEvidence: 'TOPAZ-1: Improved OS in biliary tract cancer' },
+        { id: 'combo-imatinib-gist', name: 'Imatinib (GIST)',
+            components: ['Imatinib'],
+            synergisticEffect: 1.6, cancerTypes: ['GIST'],
+            clinicalEvidence: '85% clinical benefit rate, transformed prognosis' },
+        { id: 'combo-avapritinib-gist', name: 'Avapritinib (PDGFRA D842V)',
+            components: ['Avapritinib'],
+            synergisticEffect: 1.55, cancerTypes: ['GIST (PDGFRA D842V)'],
+            clinicalEvidence: 'NAVIGATOR: 88% ORR in D842V mutant GIST' },
+        { id: 'combo-selpercatinib-ret', name: 'Selpercatinib (RET+)',
+            components: ['Selpercatinib'],
+            synergisticEffect: 1.5, cancerTypes: ['Thyroid (RET+)', 'NSCLC (RET+)'],
+            clinicalEvidence: 'LIBRETTO-001: 85% response rate' },
+        { id: 'combo-larotrectinib-ntrk', name: 'Larotrectinib (NTRK+)',
+            components: ['Larotrectinib'],
+            synergisticEffect: 1.6, cancerTypes: ['NTRK Fusion+ (Agnostic)'],
+            clinicalEvidence: '79% ORR across tumor types' }
     ];
     // ═══════════════════════════════════════════════════════════════════════════════
     // TREATMENT PROTOCOLS (Expanded)
@@ -846,7 +1500,355 @@ export class CancerTreatmentCapabilityModule {
             organization: 'NCCN', cancerType: 'Kaposi Sarcoma', stage: 'All',
             treatmentModalities: ['ART Optimization', 'Liposomal Doxorubicin', 'Paclitaxel', 'Pomalidomide'],
             efficacyScore: 0.75, sideEffectProfile: ['Myelosuppression', 'Cardiotoxicity'],
-            references: ['AIDS Malignancy Consortium'] }
+            references: ['AIDS Malignancy Consortium'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // PEDIATRIC CANCER PROTOCOLS (COG - Children's Oncology Group)
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'cog-all-standard', name: 'Pediatric ALL Standard Risk',
+            organization: 'Other', cancerType: 'Pediatric ALL', stage: 'Standard Risk',
+            treatmentModalities: ['Induction (VCR/Pred/Asp/Dauno)', 'Consolidation', 'Interim Maintenance', 'Delayed Intensification', 'Maintenance'],
+            efficacyScore: 0.95, sideEffectProfile: ['Infection', 'Mucositis', 'Neurotoxicity', 'Osteonecrosis'],
+            references: ['COG AALL0434', 'COG AALL0232', '95% 5-year survival'] },
+        { id: 'cog-all-high', name: 'Pediatric ALL High Risk',
+            organization: 'Other', cancerType: 'Pediatric ALL', stage: 'High Risk',
+            treatmentModalities: ['Intensive Induction', 'High-Dose Methotrexate', 'CAR-T Eligible', 'Blinatumomab', 'Inotuzumab', 'Transplant Evaluation'],
+            efficacyScore: 0.88, sideEffectProfile: ['Severe Myelosuppression', 'CRS', 'ICANS'],
+            references: ['COG AALL1231', 'ELIANA'] },
+        { id: 'cog-neuroblastoma-lr', name: 'Neuroblastoma Low Risk',
+            organization: 'Other', cancerType: 'Neuroblastoma', stage: 'Low Risk',
+            treatmentModalities: ['Observation', 'Surgery Alone', 'Minimal Chemotherapy if symptomatic'],
+            efficacyScore: 0.98, sideEffectProfile: ['Surgical Complications'],
+            references: ['COG ANBL0531', '>95% survival'] },
+        { id: 'cog-neuroblastoma-hr', name: 'Neuroblastoma High Risk',
+            organization: 'Other', cancerType: 'Neuroblastoma', stage: 'High Risk',
+            treatmentModalities: ['Induction Chemo', 'Tandem Transplant', 'Radiation', 'Anti-GD2 Immunotherapy', 'Isotretinoin', 'Difluoromethylornithine'],
+            efficacyScore: 0.65, sideEffectProfile: ['Pain', 'Capillary Leak', 'Long-term Effects'],
+            references: ['COG ANBL1232', 'ANBL12P1'] },
+        { id: 'cog-wilms-favorable', name: 'Wilms Tumor Favorable Histology',
+            organization: 'Other', cancerType: 'Wilms Tumor', stage: 'I-II Favorable',
+            treatmentModalities: ['Nephrectomy', 'Vincristine', 'Actinomycin-D'],
+            efficacyScore: 0.95, sideEffectProfile: ['Nausea', 'Hepatotoxicity'],
+            references: ['AREN0533', '>90% survival'] },
+        { id: 'cog-wilms-unfavorable', name: 'Wilms Tumor Unfavorable/Anaplastic',
+            organization: 'Other', cancerType: 'Wilms Tumor', stage: 'III-IV or Anaplastic',
+            treatmentModalities: ['Nephrectomy', 'Intensive Chemo (VAD regimen)', 'Radiation', 'Carboplatin/Etoposide'],
+            efficacyScore: 0.75, sideEffectProfile: ['Cardiotoxicity', 'Nephrotoxicity', 'Infertility'],
+            references: ['AREN0321'] },
+        { id: 'cog-medulloblastoma-standard', name: 'Medulloblastoma Standard Risk',
+            organization: 'Other', cancerType: 'Medulloblastoma', stage: 'Standard Risk',
+            treatmentModalities: ['Maximal Safe Resection', 'Craniospinal Radiation (Reduced)', 'Cisplatin/Vincristine/Lomustine'],
+            efficacyScore: 0.85, sideEffectProfile: ['Cognitive Effects', 'Endocrine Dysfunction', 'Hearing Loss'],
+            references: ['ACNS0331', 'SJMB03'] },
+        { id: 'cog-osteosarcoma', name: 'Osteosarcoma Pediatric Protocol',
+            organization: 'Other', cancerType: 'Osteosarcoma', stage: 'Localized/Metastatic',
+            treatmentModalities: ['Neoadjuvant MAP', 'Limb-Salvage Surgery', 'Adjuvant MAP', 'Mifamurtide (Europe)'],
+            efficacyScore: 0.72, sideEffectProfile: ['Ototoxicity', 'Cardiotoxicity', 'Nephrotoxicity'],
+            references: ['EURAMOS-1', 'INT-0133'] },
+        { id: 'cog-ewing', name: 'Ewing Sarcoma Protocol',
+            organization: 'Other', cancerType: 'Ewing Sarcoma', stage: 'All',
+            treatmentModalities: ['VDC/IE Alternating', 'Surgery or Radiation', 'High-Dose Therapy for High Risk'],
+            efficacyScore: 0.70, sideEffectProfile: ['Myelosuppression', 'Cardiotoxicity', 'Secondary Malignancy'],
+            references: ['COG AEWS1031', 'Euro-EWING'] },
+        { id: 'cog-rhabdomyosarcoma-lr', name: 'Rhabdomyosarcoma Low Risk',
+            organization: 'Other', cancerType: 'Rhabdomyosarcoma', stage: 'Low Risk',
+            treatmentModalities: ['VAC Chemotherapy', 'Local Control (Surgery/RT)'],
+            efficacyScore: 0.90, sideEffectProfile: ['Myelosuppression', 'Growth Effects'],
+            references: ['ARST0331', 'D9602'] },
+        { id: 'cog-retinoblastoma', name: 'Retinoblastoma Protocol',
+            organization: 'Other', cancerType: 'Retinoblastoma', stage: 'All',
+            treatmentModalities: ['Intra-arterial Chemotherapy', 'Focal Therapy', 'Systemic Chemo (VEC)', 'Enucleation if needed'],
+            efficacyScore: 0.96, sideEffectProfile: ['Vision Loss', 'Secondary Tumors (Rb1 carriers)'],
+            references: ['ARET0231'] },
+        { id: 'cog-hepatoblastoma', name: 'Hepatoblastoma Protocol',
+            organization: 'Other', cancerType: 'Hepatoblastoma', stage: 'All',
+            treatmentModalities: ['Cisplatin/5-FU/Vincristine', 'Surgical Resection', 'Liver Transplant if unresectable'],
+            efficacyScore: 0.85, sideEffectProfile: ['Ototoxicity', 'Nephrotoxicity'],
+            references: ['AHEP0731', 'SIOPEL-6'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // ELDERLY AND FRAIL PATIENT PROTOCOLS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'elderly-aml', name: 'AML in Elderly/Unfit',
+            organization: 'NCCN', cancerType: 'AML', stage: 'Unfit for Intensive',
+            treatmentModalities: ['Venetoclax + Azacitidine', 'Low-Dose Cytarabine', 'Glasdegib + LDAC', 'Best Supportive Care'],
+            efficacyScore: 0.55, sideEffectProfile: ['Reduced intensity toxicity', 'Infection risk'],
+            references: ['VIALE-A', 'BRIGHT AML 1003'] },
+        { id: 'elderly-breast', name: 'Breast Cancer Elderly Frail',
+            organization: 'ESMO', cancerType: 'Breast', stage: 'Frail Elderly',
+            treatmentModalities: ['Endocrine Therapy Alone (HR+)', 'Omit Radiation if low risk', 'Single-agent Chemo if needed'],
+            efficacyScore: 0.80, sideEffectProfile: ['Minimized toxicity'],
+            references: ['PRIME II', 'CALGB 9343'] },
+        { id: 'elderly-dlbcl', name: 'DLBCL Frail/Elderly',
+            organization: 'NCCN', cancerType: 'DLBCL', stage: 'Unfit',
+            treatmentModalities: ['R-mini-CHOP', 'R-GCVP', 'Polatuzumab-BR', 'Loncastuximab'],
+            efficacyScore: 0.60, sideEffectProfile: ['Reduced cardiotoxicity', 'Myelosuppression'],
+            references: ['LNH03-7B'] },
+        { id: 'elderly-myeloma', name: 'Multiple Myeloma Frail',
+            organization: 'ESMO', cancerType: 'Multiple Myeloma', stage: 'Frail',
+            treatmentModalities: ['VRd-lite', 'Rd (Lenalidomide/Dex)', 'Daratumumab-Rd', 'Dose-adjusted regimens'],
+            efficacyScore: 0.70, sideEffectProfile: ['Reduced neuropathy', 'Infection risk'],
+            references: ['MAIA', 'FIRST'] },
+        { id: 'elderly-lung', name: 'NSCLC Elderly/PS2',
+            organization: 'NCCN', cancerType: 'NSCLC', stage: 'Elderly PS2',
+            treatmentModalities: ['Single-agent Pembrolizumab (PD-L1≥50%)', 'Single-agent Docetaxel', 'TKI if driver+', 'BSC'],
+            efficacyScore: 0.55, sideEffectProfile: ['Minimized toxicity'],
+            references: ['KEYNOTE-024', 'Elderly subset analyses'] },
+        { id: 'elderly-colorectal', name: 'Colorectal Cancer Elderly',
+            organization: 'ESMO', cancerType: 'Colorectal', stage: 'Elderly/Frail',
+            treatmentModalities: ['5-FU/Leucovorin alone', 'Capecitabine monotherapy', 'Bevacizumab + reduced chemo'],
+            efficacyScore: 0.65, sideEffectProfile: ['Reduced intensity'],
+            references: ['FOCUS2', 'AVEX'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // PREGNANCY-COMPATIBLE CANCER TREATMENTS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'pregnancy-breast', name: 'Breast Cancer in Pregnancy',
+            organization: 'ESMO', cancerType: 'Breast', stage: 'Pregnancy',
+            treatmentModalities: ['Surgery (any trimester)', 'AC Chemotherapy (2nd/3rd trimester)', 'No Radiation during pregnancy', 'Endocrine after delivery'],
+            efficacyScore: 0.85, sideEffectProfile: ['Fetal monitoring required', 'Delivery timing optimization'],
+            references: ['German Breast Group Registry', 'Pregnancy-associated breast cancer guidelines'] },
+        { id: 'pregnancy-cervical', name: 'Cervical Cancer in Pregnancy',
+            organization: 'ESMO', cancerType: 'Cervical', stage: 'Pregnancy',
+            treatmentModalities: ['Conization (early stage)', 'Neoadjuvant Chemo (BOMP-EMA)', 'Delay definitive treatment', 'Delivery then treatment'],
+            efficacyScore: 0.80, sideEffectProfile: ['Preterm delivery risk', 'Close surveillance'],
+            references: ['ESGO Guidelines'] },
+        { id: 'pregnancy-lymphoma', name: 'Hodgkin Lymphoma in Pregnancy',
+            organization: 'ESMO', cancerType: 'Hodgkin Lymphoma', stage: 'Pregnancy',
+            treatmentModalities: ['ABVD (2nd/3rd trimester)', 'Single-agent Vinblastine (1st trimester if urgent)', 'Delay if possible'],
+            efficacyScore: 0.85, sideEffectProfile: ['Fetal monitoring', 'No Bleomycin if possible'],
+            references: ['European guidelines on pregnancy and cancer'] },
+        { id: 'pregnancy-melanoma', name: 'Melanoma in Pregnancy',
+            organization: 'NCCN', cancerType: 'Melanoma', stage: 'Pregnancy',
+            treatmentModalities: ['Surgical excision', 'SLNB (2nd trimester+)', 'Defer systemic therapy if possible', 'Checkpoint inhibitors contraindicated'],
+            efficacyScore: 0.75, sideEffectProfile: ['Limited systemic options'],
+            references: ['NCCN Melanoma Guidelines - Pregnancy section'] },
+        { id: 'pregnancy-thyroid', name: 'Thyroid Cancer in Pregnancy',
+            organization: 'Other', cancerType: 'Thyroid', stage: 'Pregnancy',
+            treatmentModalities: ['Surgery (2nd trimester preferred)', 'TSH suppression with levothyroxine', 'No RAI during pregnancy', 'Post-delivery RAI'],
+            efficacyScore: 0.95, sideEffectProfile: ['Minimal with proper timing'],
+            references: ['ATA Guidelines 2015'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // RELAPSED/REFRACTORY PROTOCOLS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'relapsed-dlbcl', name: 'Relapsed/Refractory DLBCL',
+            organization: 'NCCN', cancerType: 'DLBCL', stage: 'R/R',
+            treatmentModalities: ['CAR-T (Axi-cel, Liso-cel, Tisa-cel)', 'Polatuzumab-BR', 'Loncastuximab', 'Selinexor', 'Tafasitamab-Len', 'Bispecifics (Glofitamab, Epcoritamab)'],
+            efficacyScore: 0.50, sideEffectProfile: ['CRS', 'ICANS', 'Cytopenias'],
+            references: ['ZUMA-7', 'TRANSFORM', 'LOTIS-2'] },
+        { id: 'relapsed-myeloma', name: 'Relapsed/Refractory Myeloma',
+            organization: 'NCCN', cancerType: 'Multiple Myeloma', stage: 'R/R',
+            treatmentModalities: ['CAR-T (Ide-cel, Cilta-cel)', 'Bispecifics (Teclistamab, Talquetamab)', 'Selinexor-based', 'Belantamab (if available)', 'Carfilzomib combos'],
+            efficacyScore: 0.55, sideEffectProfile: ['CRS', 'ICANS', 'Ocular toxicity', 'Skin/nail changes'],
+            references: ['KarMMa', 'CARTITUDE-1', 'MajesTEC-1'] },
+        { id: 'relapsed-all', name: 'Relapsed/Refractory ALL',
+            organization: 'NCCN', cancerType: 'ALL', stage: 'R/R',
+            treatmentModalities: ['Blinatumomab', 'Inotuzumab', 'CAR-T (Tisa-cel, Brexu-cel)', 'Nelarabine (T-ALL)', 'Clofarabine-based'],
+            efficacyScore: 0.45, sideEffectProfile: ['CRS', 'ICANS', 'VOD'],
+            references: ['TOWER', 'INO-VATE ALL'] },
+        { id: 'relapsed-chl', name: 'Relapsed Hodgkin Lymphoma',
+            organization: 'NCCN', cancerType: 'Hodgkin Lymphoma', stage: 'R/R',
+            treatmentModalities: ['Brentuximab Vedotin', 'Pembrolizumab', 'Nivolumab', 'Auto-SCT', 'Allo-SCT'],
+            efficacyScore: 0.65, sideEffectProfile: ['Neuropathy', 'Immune-related AEs'],
+            references: ['AETHERA', 'KEYNOTE-204'] },
+        { id: 'relapsed-sclc', name: 'Relapsed SCLC',
+            organization: 'NCCN', cancerType: 'SCLC', stage: 'R/R',
+            treatmentModalities: ['Topotecan', 'Lurbinectedin', 'Tarlatamab', 'CAV', 'Clinical Trials'],
+            efficacyScore: 0.35, sideEffectProfile: ['Myelosuppression', 'Fatigue'],
+            references: ['ATLANTIS', 'DeLLphi-301'] },
+        { id: 'relapsed-ovarian', name: 'Relapsed Ovarian Cancer',
+            organization: 'NCCN', cancerType: 'Ovarian', stage: 'R/R',
+            treatmentModalities: ['Platinum rechallenge (if sensitive)', 'PARP maintenance', 'Mirvetuximab (FRα+)', 'Bevacizumab', 'Liposomal Doxorubicin'],
+            efficacyScore: 0.45, sideEffectProfile: ['Neuropathy', 'Myelosuppression'],
+            references: ['AURELIA', 'SOLO2', 'MIRASOL'] },
+        { id: 'relapsed-gist', name: 'Relapsed/Resistant GIST',
+            organization: 'NCCN', cancerType: 'GIST', stage: 'R/R',
+            treatmentModalities: ['Sunitinib', 'Regorafenib', 'Ripretinib', 'Avapritinib (PDGFRA)', 'Clinical Trials'],
+            efficacyScore: 0.50, sideEffectProfile: ['Hand-foot syndrome', 'Hypertension', 'Fatigue'],
+            references: ['INVICTUS', 'NAVIGATOR'] },
+        { id: 'relapsed-melanoma', name: 'Relapsed/Resistant Melanoma',
+            organization: 'NCCN', cancerType: 'Melanoma', stage: 'R/R post-ICI',
+            treatmentModalities: ['Lifileucel (TIL)', 'BRAF/MEK if BRAF+', 'LAG-3 combo', 'Clinical Trials (STING, oncolytic)'],
+            efficacyScore: 0.40, sideEffectProfile: ['Varies by therapy'],
+            references: ['C-144-01'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // TUMOR-AGNOSTIC PROTOCOLS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'agnostic-msi-h', name: 'MSI-H/dMMR Agnostic',
+            organization: 'FDA', cancerType: 'MSI-H Any Tumor', stage: 'All',
+            treatmentModalities: ['Pembrolizumab', 'Dostarlimab'],
+            efficacyScore: 0.55, sideEffectProfile: ['Immune-related AEs'],
+            references: ['KEYNOTE-158', 'GARNET'] },
+        { id: 'agnostic-tmb-h', name: 'TMB-High Agnostic',
+            organization: 'FDA', cancerType: 'TMB-H Any Tumor', stage: 'All',
+            treatmentModalities: ['Pembrolizumab'],
+            efficacyScore: 0.40, sideEffectProfile: ['Immune-related AEs'],
+            references: ['KEYNOTE-158 TMB cohort'] },
+        { id: 'agnostic-ntrk', name: 'NTRK Fusion Agnostic',
+            organization: 'FDA', cancerType: 'NTRK Fusion Any Tumor', stage: 'All',
+            treatmentModalities: ['Larotrectinib', 'Entrectinib'],
+            efficacyScore: 0.75, sideEffectProfile: ['Dizziness', 'Fatigue', 'Weight gain'],
+            references: ['LOXO-TRK', 'STARTRK'] },
+        { id: 'agnostic-ret', name: 'RET Fusion Agnostic',
+            organization: 'FDA', cancerType: 'RET Fusion Any Tumor', stage: 'All',
+            treatmentModalities: ['Selpercatinib', 'Pralsetinib'],
+            efficacyScore: 0.70, sideEffectProfile: ['Hypertension', 'Transaminitis'],
+            references: ['LIBRETTO-001', 'ARROW'] },
+        { id: 'agnostic-braf-v600e', name: 'BRAF V600E Agnostic',
+            organization: 'FDA', cancerType: 'BRAF V600E Any Tumor', stage: 'All',
+            treatmentModalities: ['Dabrafenib + Trametinib'],
+            efficacyScore: 0.50, sideEffectProfile: ['Pyrexia', 'Rash', 'Fatigue'],
+            references: ['ROAR basket trial', 'NCI-MATCH'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // SUPPORTIVE & PALLIATIVE CARE PROTOCOLS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'supportive-bone-mets', name: 'Bone Metastases Management',
+            organization: 'ASCO', cancerType: 'Any with Bone Mets', stage: 'Metastatic',
+            treatmentModalities: ['Zoledronic Acid', 'Denosumab', 'Palliative Radiation', 'Vertebroplasty', 'Pain Management'],
+            efficacyScore: 0.80, sideEffectProfile: ['ONJ risk', 'Hypocalcemia'],
+            references: ['ASCO Bone Health Guidelines'] },
+        { id: 'supportive-brain-mets', name: 'Brain Metastases Management',
+            organization: 'NCCN', cancerType: 'Any with Brain Mets', stage: 'Metastatic',
+            treatmentModalities: ['SRS', 'WBRT', 'Surgery', 'Steroids', 'Systemic Therapy (CNS-penetrant)'],
+            efficacyScore: 0.60, sideEffectProfile: ['Cognitive effects', 'Radiation necrosis'],
+            references: ['NCCN CNS Metastases Guidelines'] },
+        { id: 'supportive-malignant-effusion', name: 'Malignant Effusion Management',
+            organization: 'Other', cancerType: 'Any with Effusion', stage: 'Metastatic',
+            treatmentModalities: ['Thoracentesis/Paracentesis', 'Pleurodesis', 'Indwelling Catheter', 'HIPEC (peritoneal)'],
+            efficacyScore: 0.70, sideEffectProfile: ['Procedure-related'],
+            references: ['TIME trials'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // SURVIVORSHIP PROTOCOLS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'survivor-breast', name: 'Breast Cancer Survivorship',
+            organization: 'ASCO', cancerType: 'Breast', stage: 'Post-Treatment',
+            treatmentModalities: ['Annual mammography', 'Endocrine therapy adherence', 'Bone health', 'Cardiac surveillance', 'Lymphedema management'],
+            efficacyScore: 0.95, sideEffectProfile: ['Long-term endocrine effects'],
+            references: ['ASCO Survivorship Guidelines'] },
+        { id: 'survivor-colorectal', name: 'Colorectal Cancer Survivorship',
+            organization: 'ASCO', cancerType: 'Colorectal', stage: 'Post-Treatment',
+            treatmentModalities: ['CEA monitoring', 'Colonoscopy surveillance', 'CT scans', 'Neuropathy management'],
+            efficacyScore: 0.90, sideEffectProfile: ['Bowel dysfunction', 'Neuropathy'],
+            references: ['ASCO Colorectal Survivorship'] },
+        { id: 'survivor-lymphoma', name: 'Lymphoma Survivorship',
+            organization: 'NCCN', cancerType: 'Lymphoma', stage: 'Post-Treatment',
+            treatmentModalities: ['Secondary malignancy screening', 'Cardiac surveillance', 'Thyroid monitoring', 'Fertility preservation follow-up'],
+            efficacyScore: 0.92, sideEffectProfile: ['Late effects of chemo/radiation'],
+            references: ['NCCN Survivorship Guidelines'] },
+        { id: 'survivor-pediatric', name: 'Pediatric Cancer Survivorship (COG LTFU)',
+            organization: 'Other', cancerType: 'Pediatric Cancers', stage: 'Long-Term Follow-Up',
+            treatmentModalities: ['Risk-based surveillance', 'Cardiac echo', 'Endocrine evaluation', 'Neurocognitive assessment', 'Secondary cancer screening', 'Fertility counseling'],
+            efficacyScore: 0.90, sideEffectProfile: ['Late effects of childhood treatment'],
+            references: ['COG Long-Term Follow-Up Guidelines'] },
+        { id: 'survivor-prostate', name: 'Prostate Cancer Survivorship',
+            organization: 'ASCO', cancerType: 'Prostate', stage: 'Post-Treatment',
+            treatmentModalities: ['PSA monitoring', 'ADT side effect management', 'Bone health', 'Sexual function support', 'Urinary continence'],
+            efficacyScore: 0.93, sideEffectProfile: ['ADT metabolic effects', 'ED'],
+            references: ['ASCO Prostate Survivorship'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // QUALITY OF LIFE PROTOCOLS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'qol-fatigue', name: 'Cancer-Related Fatigue Management',
+            organization: 'NCCN', cancerType: 'Any', stage: 'Any',
+            treatmentModalities: ['Exercise prescription', 'Sleep hygiene', 'Treat anemia/depression', 'Psychostimulants if severe'],
+            efficacyScore: 0.75, sideEffectProfile: ['Minimal'],
+            references: ['NCCN Cancer-Related Fatigue Guidelines'] },
+        { id: 'qol-pain', name: 'Cancer Pain Management',
+            organization: 'NCCN', cancerType: 'Any', stage: 'Any',
+            treatmentModalities: ['WHO Pain Ladder', 'Opioid rotation', 'Interventional procedures', 'Palliative radiation', 'Integrative approaches'],
+            efficacyScore: 0.85, sideEffectProfile: ['Opioid side effects'],
+            references: ['NCCN Adult Cancer Pain'] },
+        { id: 'qol-nausea', name: 'Chemotherapy-Induced Nausea/Vomiting',
+            organization: 'ASCO', cancerType: 'Any on Chemo', stage: 'Any',
+            treatmentModalities: ['5-HT3 antagonists', 'NK1 antagonists', 'Dexamethasone', 'Olanzapine'],
+            efficacyScore: 0.90, sideEffectProfile: ['Constipation', 'QT prolongation'],
+            references: ['ASCO Antiemetic Guidelines'] },
+        { id: 'qol-neuropathy', name: 'Chemotherapy-Induced Peripheral Neuropathy',
+            organization: 'ASCO', cancerType: 'Any', stage: 'Any',
+            treatmentModalities: ['Duloxetine', 'Gabapentin', 'Physical therapy', 'Dose modification', 'Cryotherapy (prevention)'],
+            efficacyScore: 0.60, sideEffectProfile: ['Drowsiness'],
+            references: ['ASCO CIPN Guidelines'] },
+        { id: 'qol-psychosocial', name: 'Psychosocial Distress Management',
+            organization: 'NCCN', cancerType: 'Any', stage: 'Any',
+            treatmentModalities: ['Distress screening', 'Counseling', 'Support groups', 'Psychiatry referral', 'Antidepressants/anxiolytics'],
+            efficacyScore: 0.80, sideEffectProfile: ['Medication side effects if used'],
+            references: ['NCCN Distress Management'] },
+        { id: 'qol-nutrition', name: 'Cancer Nutrition Management',
+            organization: 'Other', cancerType: 'Any', stage: 'Any',
+            treatmentModalities: ['Nutritional assessment', 'Oral supplements', 'Enteral/parenteral if needed', 'Cachexia management'],
+            efficacyScore: 0.75, sideEffectProfile: ['GI intolerance'],
+            references: ['ESPEN Cancer Nutrition Guidelines'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // SPECIAL POPULATION PROTOCOLS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'special-hiv', name: 'Cancer in HIV/AIDS Patients',
+            organization: 'NCCN', cancerType: 'Any in HIV+', stage: 'Any',
+            treatmentModalities: ['Optimize ART', 'Standard cancer treatment when possible', 'Drug-drug interaction check', 'Infectious prophylaxis'],
+            efficacyScore: 0.75, sideEffectProfile: ['Drug interactions', 'Immunosuppression'],
+            references: ['NCI HIV/AIDS Malignancy Guidelines'] },
+        { id: 'special-transplant-cancer', name: 'Cancer in Transplant Recipients',
+            organization: 'Other', cancerType: 'Any post-transplant', stage: 'Any',
+            treatmentModalities: ['Reduce immunosuppression if possible', 'Switch to mTOR inhibitor', 'Standard cancer therapy with caution', 'Consider rejection risk'],
+            efficacyScore: 0.65, sideEffectProfile: ['Rejection risk', 'Infection'],
+            references: ['Transplant oncology consensus'] },
+        { id: 'special-dialysis', name: 'Cancer in Dialysis Patients',
+            organization: 'Other', cancerType: 'Any on Dialysis', stage: 'Any',
+            treatmentModalities: ['Dose-adjusted chemotherapy', 'Dialysis timing coordination', 'RCC screening', 'Consider transplant candidacy'],
+            efficacyScore: 0.60, sideEffectProfile: ['Altered pharmacokinetics'],
+            references: ['Renal impairment dosing guidelines'] },
+        { id: 'special-liver-impaired', name: 'Cancer with Liver Dysfunction',
+            organization: 'Other', cancerType: 'Any with Liver Dysfunction', stage: 'Any',
+            treatmentModalities: ['Child-Pugh adjusted dosing', 'Avoid hepatotoxic agents', 'Close LFT monitoring'],
+            efficacyScore: 0.55, sideEffectProfile: ['Hepatotoxicity risk'],
+            references: ['Hepatic impairment dosing guidelines'] },
+        { id: 'special-adolescent-young-adult', name: 'Adolescent/Young Adult (AYA) Cancer',
+            organization: 'NCCN', cancerType: 'AYA Cancers (15-39)', stage: 'Any',
+            treatmentModalities: ['Age-appropriate protocols', 'Fertility preservation', 'Psychosocial support', 'Financial navigation', 'Transition planning'],
+            efficacyScore: 0.85, sideEffectProfile: ['Long-term survivorship issues'],
+            references: ['NCCN AYA Oncology'] },
+        { id: 'special-second-primary', name: 'Second Primary Malignancy',
+            organization: 'Other', cancerType: 'Second Primary Cancer', stage: 'Any',
+            treatmentModalities: ['Treat as new primary', 'Consider prior treatment toxicities', 'Cumulative dose limits', 'Genetic evaluation'],
+            efficacyScore: 0.70, sideEffectProfile: ['Prior treatment effects'],
+            references: ['Second malignancy management guidelines'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // ETHNIC AND POPULATION-SPECIFIC CONSIDERATIONS
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'ethnic-pharmacogenomics', name: 'Pharmacogenomic-Guided Therapy',
+            organization: 'FDA', cancerType: 'Any', stage: 'Any',
+            treatmentModalities: ['DPYD testing (5-FU)', 'UGT1A1 testing (Irinotecan)', 'TPMT/NUDT15 (Thiopurines)', 'G6PD (Rasburicase)'],
+            efficacyScore: 0.90, sideEffectProfile: ['Prevents severe toxicity'],
+            references: ['CPIC Guidelines', 'FDA drug labels'] },
+        { id: 'ethnic-asian-egfr', name: 'EGFR in East Asian NSCLC',
+            organization: 'Other', cancerType: 'NSCLC (East Asian)', stage: 'Any',
+            treatmentModalities: ['Higher EGFR mutation rate (~50%)', 'First-line TKI', 'Osimertinib preferred'],
+            efficacyScore: 0.85, sideEffectProfile: ['Standard TKI toxicities'],
+            references: ['Asian NSCLC molecular epidemiology'] },
+        { id: 'ethnic-tnbc-african', name: 'TNBC in African Descent',
+            organization: 'Other', cancerType: 'TNBC (African descent)', stage: 'Any',
+            treatmentModalities: ['Higher incidence', 'Standard TNBC protocols', 'Ensure access to immunotherapy', 'Clinical trial enrollment'],
+            efficacyScore: 0.75, sideEffectProfile: ['Standard toxicities'],
+            references: ['Cancer disparities research'] },
+        { id: 'ethnic-multiple-myeloma-african', name: 'Multiple Myeloma in African Descent',
+            organization: 'Other', cancerType: 'Multiple Myeloma (African descent)', stage: 'Any',
+            treatmentModalities: ['2x higher incidence', 'Standard MM protocols', 'Consider earlier transplant', 'Equal access to novel therapies'],
+            efficacyScore: 0.75, sideEffectProfile: ['Standard toxicities'],
+            references: ['Myeloma disparities literature'] },
+        // ═══════════════════════════════════════════════════════════════════════════════
+        // PREVENTION AND RISK REDUCTION
+        // ═══════════════════════════════════════════════════════════════════════════════
+        { id: 'prevention-brca-rrso', name: 'BRCA Risk-Reducing Surgery',
+            organization: 'NCCN', cancerType: 'BRCA1/2 Carrier', stage: 'Prevention',
+            treatmentModalities: ['Risk-reducing salpingo-oophorectomy', 'Risk-reducing mastectomy', 'Enhanced surveillance', 'Chemoprevention options'],
+            efficacyScore: 0.95, sideEffectProfile: ['Surgical menopause', 'QoL effects'],
+            references: ['NCCN Genetic/Familial High-Risk'] },
+        { id: 'prevention-lynch-colon', name: 'Lynch Syndrome Surveillance',
+            organization: 'NCCN', cancerType: 'Lynch Syndrome', stage: 'Prevention',
+            treatmentModalities: ['Colonoscopy q1-2 years from age 20-25', 'Consider prophylactic hysterectomy/BSO', 'Aspirin (investigational)'],
+            efficacyScore: 0.85, sideEffectProfile: ['Procedural risks'],
+            references: ['NCCN Lynch Syndrome'] },
+        { id: 'prevention-fap', name: 'FAP Prophylactic Colectomy',
+            organization: 'NCCN', cancerType: 'FAP', stage: 'Prevention',
+            treatmentModalities: ['Prophylactic colectomy (late teens/early 20s)', 'Endoscopic surveillance', 'Sulindac/Celecoxib for adenomas'],
+            efficacyScore: 0.95, sideEffectProfile: ['Surgical morbidity'],
+            references: ['NCCN Colorectal Cancer Screening'] }
     ];
     constructor() {
         console.log('Cancer Treatment Capability Module initialized');