63. Targeted therapy - general characteristics. Targeted therapy for melanoma, prostate cancer, and non-small cell lung cancer (NSCLC).
Covers targeted therapy across three cancers: melanoma, where BRAF and MEK inhibitors act on the MAPK pathway and combination treatment is used to limit resistance; prostate cancer, where androgen receptor signalling is blocked by antagonists or reduced by synthesis inhibitors; and NSCLC, with EGFR, ALK and other driver alterations. A summary table compares the three tumour types, and the note ends with the role of molecular testing.
Topic 63 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 6 sections, about 422 words (3 min of reading), with 15 flashcards.
In this note
Targeted therapy - general characteristics. Targeted therapy for melanoma, prostate cancer, and non-small cell lung cancer (NSCLC).
I. TARGETED THERAPY FOR MELANOMA
II. TARGETED THERAPY FOR PROSTATE CANCER
III. TARGETED THERAPY FOR NON-SMALL CELL LUNG CANCER (NSCLC)
IV. COMPARISON OF TARGETED THERAPY BY TUMOR TYPE
V. ROLE OF MOLECULAR TESTING
I. TARGETED THERAPY FOR MELANOMA
Melanoma is driven by activating mutations in signaling pathways regulating cell proliferation and survival, most commonly:
MAPK (RAS–RAF–MEK–ERK) pathway
Key Molecular Targets in Melanoma
BRAF
MEK
(Less commonly: KIT in mucosal/acral melanoma)
BRAF-MUTANT MELANOMA
Most commonly BRAF V600E mutation
Causes constitutive activation of MAPK pathway
Leads to uncontrolled melanocyte proliferation
Pathogenesis
1. BRAF mutation activates RAF kinase without growth signals.
2. Continuous downstream MEK–ERK signaling.
3. Increased proliferation and survival.
4. Aggressive tumor behavior.
Targeted Strategy
BRAF inhibitors block mutant BRAF kinase
MEK inhibitors block downstream signaling
Combination therapy is standard to prevent resistance.
Why Combination Therapy Is Needed
1. BRAF inhibition alone leads to pathway reactivation.
