{
  "metadata": {
    "description": "Approved therapies and standard of care for Glioblastoma (GBM)",
    "purpose": "Ground truth baseline for Gap Analysis",
    "created_date": "2026-01-22T18:34:03.782943",
    "sources": [
      "FDA approved therapies",
      "NCCN Guidelines for CNS Cancers",
      "Published clinical guidelines"
    ]
  },
  "standard_of_care": {
    "primary_treatment": {
      "description": "Stupp Protocol (first-line treatment)",
      "components": [
        "Maximal safe surgical resection",
        "Concurrent chemoradiation (Temozolomide + RT)",
        "Adjuvant Temozolomide (6 cycles)"
      ],
      "established_year": 2005,
      "reference": "Stupp et al. NEJM 2005"
    },
    "radiation_therapy": {
      "standard_dose": "60 Gy in 30 fractions",
      "concurrent_chemo": "Temozolomide 75 mg/m2 daily"
    }
  },
  "approved_agents": [
    {
      "name": "Temozolomide",
      "brand_names": [
        "Temodar",
        "Temodal"
      ],
      "class": "Alkylating agent (DNA methylation)",
      "mechanism": "O6-methylguanine DNA damage",
      "approval_year": 1999,
      "indication": "Newly diagnosed and recurrent GBM",
      "biomarker": "MGMT methylation (predictive)",
      "route": "Oral",
      "notes": "Standard first-line chemotherapy"
    },
    {
      "name": "Bevacizumab",
      "brand_names": [
        "Avastin"
      ],
      "class": "Anti-angiogenic (VEGF inhibitor)",
      "mechanism": "Binds VEGF-A, inhibits angiogenesis",
      "approval_year": 2009,
      "indication": "Recurrent GBM (FDA); not approved in EU",
      "biomarker": null,
      "route": "IV infusion",
      "notes": "Accelerated approval; improves PFS but not OS"
    },
    {
      "name": "Lomustine (CCNU)",
      "brand_names": [
        "CeeNU",
        "Gleostine"
      ],
      "class": "Alkylating agent (nitrosourea)",
      "mechanism": "DNA cross-linking and carbamoylation",
      "approval_year": 1976,
      "indication": "Recurrent GBM, combination therapy",
      "biomarker": null,
      "route": "Oral",
      "notes": "Often used with Bevacizumab at recurrence"
    },
    {
      "name": "Carmustine (BCNU)",
      "brand_names": [
        "BiCNU"
      ],
      "class": "Alkylating agent (nitrosourea)",
      "mechanism": "DNA cross-linking",
      "approval_year": 1977,
      "indication": "GBM, brain tumors",
      "biomarker": null,
      "route": "IV infusion",
      "notes": "Used less commonly due to toxicity"
    },
    {
      "name": "Carmustine Wafer",
      "brand_names": [
        "Gliadel"
      ],
      "class": "Local chemotherapy implant",
      "mechanism": "Sustained BCNU release at resection site",
      "approval_year": 1996,
      "indication": "Newly diagnosed high-grade glioma (adjunct to surgery)",
      "biomarker": null,
      "route": "Surgical implant",
      "notes": "Modest survival benefit; limited use"
    }
  ],
  "approved_devices": [
    {
      "name": "Tumor Treating Fields (TTFields)",
      "brand_names": [
        "Optune"
      ],
      "class": "Electric field therapy device",
      "mechanism": "Alternating electric fields disrupt cell division",
      "approval_year": 2011,
      "indication": "Newly diagnosed and recurrent GBM",
      "biomarker": null,
      "notes": "Worn 18+ hours/day; added to Stupp protocol improves OS"
    }
  ],
  "emerging_approaches_under_investigation": [
    {
      "category": "Immunotherapy",
      "examples": [
        "Checkpoint inhibitors",
        "CAR-T cells",
        "Tumor vaccines",
        "Oncolytic viruses"
      ],
      "status": "Clinical trials ongoing; no approvals yet for GBM"
    },
    {
      "category": "Targeted Therapy",
      "examples": [
        "EGFR inhibitors",
        "IDH inhibitors",
        "BRAF inhibitors"
      ],
      "status": "Limited efficacy in unselected populations"
    },
    {
      "category": "Novel Delivery",
      "examples": [
        "Convection-enhanced delivery",
        "Nanoparticles",
        "BBB disruption"
      ],
      "status": "Early clinical development"
    }
  ],
  "key_biomarkers": [
    {
      "name": "MGMT promoter methylation",
      "type": "Predictive",
      "relevance": "Predicts response to temozolomide",
      "testing": "Standard in clinical practice"
    },
    {
      "name": "IDH1/2 mutation",
      "type": "Prognostic/Diagnostic",
      "relevance": "Better prognosis if mutated; reclassifies as IDH-mutant glioma",
      "testing": "Standard in clinical practice"
    },
    {
      "name": "EGFR amplification/EGFRvIII",
      "type": "Prognostic",
      "relevance": "Associated with worse prognosis; therapeutic target under investigation",
      "testing": "Variable"
    },
    {
      "name": "TERT promoter mutation",
      "type": "Diagnostic",
      "relevance": "Supports GBM diagnosis",
      "testing": "Increasingly used"
    }
  ],
  "unmet_needs": [
    "Median survival remains ~15-18 months",
    "Nearly universal recurrence",
    "Blood-brain barrier limits drug delivery",
    "Tumor heterogeneity and resistance",
    "Lack of effective immunotherapy",
    "No validated biomarkers for treatment selection (except MGMT)",
    "Limited options at recurrence"
  ]
}