Cancer Biology, Genetics, and Precision Oncology
Core concepts
Understand oncogenes versus tumor suppressors, the hallmarks of cancer, and the two-hit hypothesis. Know hereditary syndromes: BRCA1/2 (breast/ovarian/pancreatic/prostate), Lynch syndrome (MSI, colorectal/endometrial), Li-Fraumeni (TP53), APC (FAP), and MEN. Somatic versus germline testing distinctions matter for family counseling and therapy selection. Precision oncology concepts: actionable alterations, companion diagnostics, tumor mutational burden, MSI-high as a tissue-agnostic biomarker, and resistance mechanisms (e.g., EGFR T790M, ESR1). Pharmacogenomics (DPYD and 5-FU toxicity, TPMT and thiopurines, G6PD) is testable. Recognize the difference between prognostic and predictive biomarkers.
Traps
Questions test whether a finding is germline or somatic, whether a variant is actionable, and the difference between a prognostic and predictive marker. Watch for confusing BRCA-associated cancer risk with PARP inhibitor indication and for misapplying tissue-agnostic approvals.
Rule of thumb
Ask: does this alteration predict response to a specific drug (predictive) or just describe outcome (prognostic)? Only predictive markers change therapy.
Worked example
MSI-high status predicts benefit from immune checkpoint inhibitors across tumor types, making it a tissue-agnostic predictive biomarker.