@erosolaraijs/cure 1.0.6 → 2.0.0

package/src/capabilities/cancerTreatmentCapability.ts

@@ -410,7 +410,228 @@ 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)' }
   ];
 
   // ═══════════════════════════════════════════════════════════════════════════════
@@ -446,7 +667,136 @@ 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'] }
   ];
 
   // ═══════════════════════════════════════════════════════════════════════════════
@@ -480,7 +830,129 @@ 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' }
   ];
 
   // ═══════════════════════════════════════════════════════════════════════════════
@@ -992,7 +1464,226 @@ 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'] }
   ];
 
   constructor() {