PA6.2-3 | Molecular Basis of Cancer & Carcinogenesis — Summary & Reflection

REFLECT

Think about a patient from your clinical exposure (or a case you have read) with a cancer diagnosis. Based on what you now know:

1. Which hallmarks of cancer are likely to be active in that tumour type, and what molecular events might underlie them?
2. If the patient has a family history of that cancer, which model — hereditary two-hit versus acquired multistep — applies, and what screening implications follow?
3. Is there a known carcinogen associated with that cancer? How does the mechanism of that carcinogen connect to the molecular alterations you'd expect in the tumour?

Jot down two to three sentences for each question. This exercise connects the molecular framework directly to clinical pattern recognition.

KEY TAKEAWAYS

What you have covered in this module:

• Hallmarks of cancer (10) — self-sufficiency in growth, insensitivity to inhibition, evading apoptosis, limitless replication, angiogenesis, invasion/metastasis, Warburg metabolism, immune evasion, genome instability, tumour-promoting inflammation

• Oncogenes — gain-of-function mutations (point mutation, amplification, translocation); dominant; prototype examples: RAS (GTPase), MYC (transcription), HER2 (receptor kinase), ABL (tyrosine kinase)

• Tumour suppressor genes — loss-of-function; recessive at cell level; Knudson two-hit; RB (G1 checkpoint), TP53 (guardian of genome), APC (Wnt), BRCA1/2 (DNA repair)

• Apoptosis/DNA repair — BCL2 overexpression; MMR genes (Lynch/MSI); epigenetic silencing; miRNA dysregulation

• Multistep carcinogenesis — sequential driver mutations over years; colon APC→KRAS→SMAD4→TP53 model; clonal evolution + tumour heterogeneity

• Chemical carcinogens — initiation (irreversible mutation) vs promotion (reversible clonal expansion); direct-acting vs procarcinogens; PAHs→lung, β-naphthylamine→bladder, aflatoxin B1→liver TP53 hotspot

• Radiation — UV→pyrimidine dimers→NER→skin cancer; xeroderma pigmentosum; IR→DSBs→leukaemia/thyroid/breast; linear no-threshold

• Microbial carcinogens — HPV (E6/p53, E7/pRB)→cervical; HBV/HCV→HCC; EBV→Burkitt/NPC; HTLV-1→ATLL; HHV-8→Kaposi; H. pylori→gastric/MALT