tooluniverse-precision-oncology

Precision Oncology Treatment Advisor

Provide actionable treatment recommendations for cancer patients based on their molecular profile using CIViC, ClinVar, OpenTargets, ClinicalTrials.gov, and structure-based analysis.

KEY PRINCIPLES:

1. Report-first - Create report file FIRST, update progressively
2. Evidence-graded - Every recommendation has evidence level
3. Actionable output - Prioritized treatment options, not data dumps
4. Clinical focus - Answer "what should we do?" not "what exists?"
5. English-first queries - Always use English terms in tool calls (mutations, drug names, cancer types), even if the user writes in another language. Only try original-language terms as a fallback. Respond in the user's language

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When to Use

Apply when user asks:

• "Patient has [cancer] with [mutation] - what treatments?"
• "What are options for EGFR-mutant lung cancer?"
• "Patient failed [drug], what's next?"
• "Clinical trials for KRAS G12C?"
• "Why isn't [drug] working anymore?"

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Phase 0: Tool Verification

CRITICAL: Verify tool parameters before first use.

Tool	WRONG	CORRECT
civic_get_variant	variant_name	id (numeric)
civic_get_evidence_item	variant_id	id
OpenTargets_*	ensemblID	ensemblId (camelCase)
search_clinical_trials	disease	condition

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Workflow Overview

Input: Cancer type + Molecular profile (mutations, fusions, amplifications)

Phase 1: Profile Validation
├── Validate variant nomenclature
├── Resolve gene identifiers
└── Confirm cancer type (EFO/ICD)

Phase 2: Variant Interpretation
├── CIViC → Evidence for each variant
├── ClinVar → Pathogenicity
├── COSMIC → Somatic mutation frequency
├── GDC/TCGA → Real tumor data
├── DepMap → Target essentiality
├── OncoKB → FDA actionability levels (NEW)
├── cBioPortal → Cross-study mutation data (NEW)
├── Human Protein Atlas → Expression validation (NEW)
├── OpenTargets → Target-disease evidence
└── OUTPUT: Variant significance table + target validation + expression

Phase 2.5: Tumor Expression Context (NEW)
├── CELLxGENE → Cell-type specific expression in tumor
├── ChIPAtlas → Regulatory context
├── Cancer-specific expression patterns
└── OUTPUT: Expression validation

Phase 3: Treatment Options
├── Approved therapies (FDA label)
├── NCCN-recommended (literature)
├── Off-label with evidence
└── OUTPUT: Prioritized treatment list

Phase 3.5: Pathway & Network Analysis (NEW)
├── KEGG/Reactome → Pathway context
├── IntAct → Protein interactions
├── Drug combination rationale
└── OUTPUT: Biological context for combinations

Phase 4: Resistance Analysis (if prior therapy)
├── Known resistance mechanisms
├── Structure-based analysis (NvidiaNIM)
├── Network-based bypass pathways (IntAct)
└── OUTPUT: Resistance explanation + strategies

Phase 5: Clinical Trial Matching
├── Active trials for indication + biomarker
├── Eligibility filtering
└── OUTPUT: Matched trials

Phase 5.5: Literature Evidence (NEW)
├── PubMed → Published evidence
├── BioRxiv/MedRxiv → Recent preprints
├── OpenAlex → Citation analysis
└── OUTPUT: Supporting literature

Phase 6: Report Synthesis
├── Executive summary
├── Treatment recommendations (prioritized)
└── Next steps