8 modules on cutaneous melanoma: melanocyte biology, UV-driven SBS7 mutational signature, BRAF/NRAS/NF1 driver landscape, ABCDE clinical exam, AJCC 8th-edition staging, BRAF+MEK targeted therapy, and the checkpoint-blockade revolution (KEYNOTE-006, CheckMate-067).
Eight Modules
- Part I — Overview & Epidemiology: ~325 000 cases/yr globally, lifetime risk ~1 in 50 in fair-skinned populations, Australia/NZ ~5x USA, ~80% of skin-cancer deaths.
- Part II — Skin & Melanocytes: Neural crest origin, melanin biosynthesis (eumelanin vs pheomelanin), MC1R signalling, photoprotection vs photodamage.
- Part III — UV & DNA Damage: UVB pyrimidine dimers, UVA oxidative damage, COSMIC SBS7 signature, dose-response (intermittent intense exposure stronger than chronic), childhood sunburn risk.
- Part IV — Genetics: BRAF V600E (~50%), NRAS Q61 (~25%), NF1-loss (~14%), KIT, CDKN2A familial melanoma, TERT promoter mutations. PDB: 3OG7 BRAF V600E + vemurafenib.
- Part V — Clinical Presentation: ABCDE rule, four major subtypes (superficial spreading, nodular, lentigo maligna, acral lentiginous), dermoscopy 7-point checklist.
- Part VI — AJCC Staging: Breslow thickness, ulceration, mitotic rate, sentinel lymph node biopsy, the prognostic gradient.
- Part VII — Therapy (flagship): Surgical excision, BRAF+MEK combos (dabrafenib+trametinib, encorafenib+binimetinib), checkpoint blockade (pembrolizumab, nivolumab, ipilimumab; CheckMate-067 ~40% 10-yr survival in advanced disease), TIL therapy (lifileucel 2024). PDB: 3OG7, 5IUS PD-1/PD-L1.
- Part VIII — Prevention & Surveillance: Sun protection, SPF, SunSmart programmes, screening in high-risk patients, ctDNA monitoring future.
The therapy module covers the 30-year arc from cytotoxic dacarbazine (5% response) to the 40% durable-survival figures of combination ipilimumab+nivolumab in advanced melanoma — the most striking outcome shift in modern oncology.