General Oncology and Principles of Cancer Biology
Core concepts
Candidates must connect hallmarks of cancer (self-sufficiency in growth signals, insensitivity to growth inhibition, evasion of apoptosis, replicative immortality, angiogenesis, invasion/metastasis, genomic instability, immune evasion, deregulated metabolism) to clinical behaviour and drug classes. Know the oncogene vs tumour suppressor dichotomy: oncogenes (RAS, MYC, HER2, BCR-ABL) are activated by gain-of-function mutation/amplification and are dominant; tumour suppressors (TP53, RB, APC, BRCA1/2, PTEN) follow Knudson's two-hit logic and are recessive at the cell level. Understand driver vs passenger mutations, oncogene addiction, synthetic lethality (PARP inhibitors in BRCA-mutated cells), apoptosis pathways (BCL-2, p53), cell-cycle checkpoints (CDK4/6–RB axis), and signalling cascades (EGFR/RAS/RAF/MEK/ERK; PI3K/AKT/mTOR). Also grasp tumour heterogeneity and clonal evolution, cancer stem cell concepts, angiogenesis (VEGF), telomerase, mismatch repair/microsatellite instability, homologous recombination deficiency, and carcinogenesis stages (initiation, promotion, progression) with chemical, viral (HPV, EBV, HBV/HCV, HTLV-1), and radiation carcinogens.
Traps
Questions often invert oncogene/suppressor logic, present a germline syndrome (Li-Fraumeni = TP53; familial adenomatous polyposis = APC; MEN = RET/MEN1) and ask for the mutated gene, or test whether a marker is prognostic vs predictive. Distinguish germline vs somatic BRCA testing implications. Watch for 'always/never' distractors in apoptosis and cell-cycle items.
Worked example / rule of thumb
A tumour with a pathogenic BRCA1 mutation is HR-deficient; PARP inhibition blocks single-strand repair, and unrepaired single-strand breaks collapse replication forks into double-strand breaks that the cell cannot fix - synthetic lethality. Rule of thumb: oncogene = gain of function, one hit enough; suppressor = loss of function, usually two hits.