Cutaneous Melanoma
Malignant Melanoma of Skin
From melanocyte biology and UV photochemistry to BRAF inhibitors, anti-PD-1 antibodies and TIL therapy — eight integrating modules.
Why a course on melanoma?
Cutaneous melanoma is the cancer most disproportionate between incidence and lethality: it accounts for fewer than 3% of skin cancers yet causes roughly 80% of skin-cancer deaths. With ~325,000 new cases per year worldwide (GLOBOCAN 2020) and a lifetime risk that has risen ~4× in fair-skinned populations since the 1970s, it is also the cancer whose epidemiology has been rewritten by a behavioural exposure: ultraviolet radiation.
And yet, in the last fifteen years melanoma has gone from one of the most chemotherapy-resistant cancers known — median survival in stage IV was ~6 months — to a flagship of precision and immune oncology. The course traces the mutagenic biochemistry, the molecular oncogenic drivers, the AJCC 8 staging system, BRAF/MEK targeted combinations, anti-PD-1/anti-CTLA-4 checkpoint blockade, and the 2024 approval of TIL therapy. It cross-references Cancer, Hallmarks, Oncogenes, and Pharmacology.
Course Parts
Overview & Epidemiology
A cancer of melanocytes: ~325,000 cases/year globally, ~1-in-50 lifetime risk in fair-skinned populations, Australia/NZ ~5x USA, ~80% of skin-cancer deaths from <3% of skin cancers.
Skin Anatomy & Melanocytes
Epidermis layers, neural-crest origin of melanocytes, dendritic morphology, melanin biosynthesis (eumelanin vs pheomelanin), MC1R signalling, the melanin unit.
UV Radiation & DNA Damage
UVB (290–320 nm) vs UVA (320–400 nm), CPD and 6-4 photoproducts, oxidative damage, COSMIC SBS7 signature, intermittent intense exposure, childhood sunburn risk.
Genetics & Molecular Drivers
BRAF V600E (~50%), NRAS Q61 (~25%), NF1-loss (~14%), KIT (acral/mucosal), CDKN2A (familial), MITF, TERT promoter — the commonest non-coding driver in any cancer.
Clinical Presentation
ABCDE rule, four major subtypes (superficial spreading, nodular, lentigo maligna, acral lentiginous), differential, dermoscopy 7-point checklist, reflectance confocal microscopy.
Staging
AJCC 8th edition (2018): Breslow thickness, ulceration, mitotic rate (T); sentinel-node N staging; M1a–d by metastasis site; LDH; the prognostic gradient.
Therapy
Wide local excision, MSLT-II sentinel biopsy, BRAF+MEK combinations (dabrafenib+trametinib, encorafenib+binimetinib), anti-PD-1, ipi/nivo, TIL therapy (lifileucel 2024), T-VEC.
Prevention & Surveillance
Sun protection, SPF, SunSmart programs, whole-body skin exam, screening evidence, pediatric and pregnancy melanoma, ctDNA monitoring of the future.
What you’ll learn
- Distinguish UV-induced from non-UV (acral, mucosal, uveal) melanoma at the genomic level.
- Trace MC1R → cAMP → MITF → tyrosinase signalling in melanin biosynthesis.
- Read a COSMIC SBS7 mutational signature and recognise the C>T at dipyrimidines fingerprint.
- Apply the ABCDE rule and dermoscopic 7-point checklist at the bedside.
- Stage a melanoma under AJCC 8 using Breslow thickness, ulceration, and SLN status.
- Choose between BRAF+MEK vs anti-PD-1 vs ipi/nivo for stage III/IV disease.
- Recognise immune-related adverse events from checkpoint blockade.
- Counsel a patient on sun protection grounded in the SunSmart evidence base.
Prerequisites
Working knowledge of cell-cycle regulation, MAPK/PI3K signalling, and basic adaptive immunity. The course cross-references Cancer, Cancer Hallmarks, Oncogenes, and Pharmacology.