Science of Oncology: Carcinogenesis, Gene Classes, Growth Kinetics, and Metastasis
The central framework
Carcinogenesis is a multistep process of initiation (irreversible DNA damage), promotion (clonal expansion of the initiated cell), and progression (accumulating alterations and invasive capacity). Questions usually test whether you can assign a gene or process to the correct functional class.
Genes and pathways
- Oncogenes act dominantly: one activating mutation, amplification, or translocation suffices. Examples: RAS, MYC, HER2/ERBB2, EGFR, BCR-ABL.
- Tumor suppressors are recessive at the cellular level (Knudson two-hit): both alleles must be lost or silenced. Examples: TP53, RB1, APC, PTEN, BRCA1/2.
- Checkpoints: the G1/S restriction point (RB–E2F, p53–p21) and G2/M. Drug sensitivity tracks with proliferative fraction and cell-cycle phase.
Hallmarks of cancer
Sustained proliferation, evasion of growth suppressors, resistance to apoptosis, replicative immortality (telomerase), induced angiogenesis, invasion and metastasis, genomic instability, immune evasion, deregulated metabolism (Warburg effect), and tumor-promoting inflammation.
Growth kinetics and metastasis
Tumors follow roughly Gompertzian growth: the growth fraction falls as mass rises. The log-kill hypothesis states that a dose kills a constant fraction, not a constant number, of cells - which is why adjuvant therapy against microscopic residual disease outperforms the same regimen against bulky disease. Metastasis requires epithelial–mesenchymal transition, intravasation, survival in circulation, extravasation, and colonization of a permissive niche ("seed and soil").
Worked example
A tumor shows biallelic BRCA1 loss with no detectable protein. That is a tumor suppressor pattern causing homologous-recombination deficiency, predicting sensitivity to platinum agents and PARP inhibitors.
Rule of thumb: oncogene = stuck accelerator (one hit); tumor suppressor = failed brakes (usually two hits).