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

• "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

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 -> Resolve gene IDs (Ensembl, UniProt, ChEMBL)
Phase 2: Variant Interpretation -> CIViC, ClinVar, COSMIC, GDC/TCGA, DepMap, OncoKB, cBioPortal, HPA
Phase 2.5: Tumor Expression -> CELLxGENE cell-type expression, ChIPAtlas regulatory context
Phase 3: Treatment Options -> OpenTargets + DailyMed (approved), ChEMBL (off-label)
Phase 3.5: Pathway & Network -> KEGG/Reactome pathways, IntAct interactions
Phase 4: Resistance Analysis -> CIViC + PubMed + NvidiaNIM structure analysis
Phase 5: Clinical Trials -> ClinicalTrials.gov search + eligibility
Phase 5.5: Literature -> PubMed, BioRxiv/MedRxiv preprints, OpenAlex citations
Phase 6: Report Synthesis -> Executive summary + prioritized recommendations

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Key Tools by Phase

Phase 1: Profile Validation

• MyGene_query_genes - Resolve gene to Ensembl ID
• UniProt_search - Get UniProt accession
• ChEMBL_search_targets - Get ChEMBL target ID

Phase 2: Variant Interpretation

• civic_search_variants / civic_get_variant - CIViC evidence
• COSMIC_get_mutations_by_gene / COSMIC_search_mutations - Somatic mutations
• GDC_get_mutation_frequency / GDC_get_ssm_by_gene - TCGA patient data
• GDC_get_gene_expression / GDC_get_cnv_data - Expression and CNV
• DepMap_get_gene_dependencies / DepMap_get_drug_response - Target essentiality
• OncoKB_annotate_variant / OncoKB_get_gene_info - Actionability
• cBioPortal_get_mutations / cBioPortal_get_cancer_studies - Cross-study data
• HPA_search_genes_by_query / HPA_get_comparative_expression_by_gene_and_cellline - Expression

Phase 2.5: Tumor Expression

• CELLxGENE_get_expression_data / CELLxGENE_get_cell_metadata - Cell-type expression

Phase 3: Treatment Options

• OpenTargets_get_associated_drugs_by_target_ensemblId - Approved drugs
• DailyMed_search_spls - FDA label details
• ChEMBL_get_drug_mechanisms_of_action_by_chemblId - Drug mechanism

Phase 3.5: Pathway & Network

• kegg_find_genes / kegg_get_gene_info - KEGG pathways
• reactome_disease_target_score - Reactome disease relevance
• intact_get_interaction_network - Protein interactions

Phase 4: Resistance Analysis

• civic_search_evidence_items - Resistance evidence (clinical_significance="Resistance")
• PubMed_search_articles - Resistance literature
• NvidiaNIM_alphafold2 / NvidiaNIM_diffdock - Structure-based analysis

Phase 5: Clinical Trials

• search_clinical_trials - Find trials (param: condition, NOT disease)
• get_clinical_trial_eligibility_criteria - Eligibility details

Phase 5.5: Literature

• PubMed_search_articles - Published evidence
• BioRxiv_search_preprints / MedRxiv_search_preprints - Preprints (flag as NOT peer-reviewed)
• openalex_search_works - Citation analysis

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References

• TOOLS_REFERENCE.md - Complete tool documentation with parameters and examples
• API_USAGE_PATTERNS.md - Detailed code examples for each phase
• TREATMENT_ALGORITHMS.md - Evidence grading, treatment prioritization, cancer type mappings, DepMap interpretation
• REPORT_TEMPLATE.md - Report template with output tables
• EXAMPLES.md - Worked examples (EGFR NSCLC, T790M resistance, KRAS G12C, no actionable mutations)
• CHECKLIST.md - Quality and completeness checklist