Melanoma 💢

Question 1

Types and prevalence of different skin cancers 3

Answer 1

1. Basal Call Carinoma (BCC)
   = most common 8/10, low metastatic potential.
2. Squamous cell carcinoma (SCC)
   = 2/10
   = Can develop in sites of chronic wounds, inflammation or scarring
3. Melanoma

Question 2

Risk Factors of skin cancers

Answer 2

1. NON MELANOMA =
   UV exposure
   MALES
2. MELANOMA =
   UV
   PRONENESS TO NEVI
   FAMILY HISTORY

Question 3

Prevention of BCC and Scc

Answer 3

Sun protection
Oral nicotinamide (vit B3)
TOPICAL flurouracil

Question 4

Explain the pathophysiology of cutaneous melanoma

At Genetic level and Protein Level

Answer 4

Genetic level =
A. Activating BRAF mutation = benign formation
B. Mutations in the TERT promoter = stage 0 melanoma
C. Mutations in cell-cycle controlling gene CDKN2A =
invasive potential

Target therapy- BRAF/MEK Inhibitors

Question 5

Pathophysiology of cutaneous melanoma
At protein level

Answer 5

A. Over summation of MAPK pathway
B. Mutations at PTEN = metastasis

Target therapy- BRAF/MEK Inhibitors

Question 6

Explain ADAPTIVE IMMUNE RESISTANCE

In early response in lymph nodes

Answer 6

After T activation
CTLA-4 is stored in intracellular vesicles and then recruited to T cell surface to inhibit further t cell proliferation

Immunotherapy/checkpoint inhibiton:
Monoclonal antibodies against CLTA-4, PD1, PD-L1

Question 7

Explain ADAPTIVE IMMUNE RESISTANCE

In late response in peripherals

Answer 7

T cells release interferon and trigger JAK-STAT expression of ligand (PD-L1) on surface of melanoma cells

Binding of PD-L1 (melanoma cell) to PD-1 (T cell) = suppression of t cell anti tumour response

Question 8

Name the 4 genetic melanoma subtypes

Answer 8

1. BRAF mutant melanomas (50%)
2. N-Ras mutant and H-Ras- mutant (25%)
3. NF1 mutant (15%)
4. Triple wild type (10%)

Question 9

Checkpoint inhibition therapy
DRUGS

Answer 9

Ipilimumab => CTLA-4

Pembrolizumab => PD-1

Nivolumab => PD-1

Question 10

Challenges in management of

TARGET THERAPY

Answer 10

Development of resistance (while on therapy is common)

RESISTANCE against BRAF and MEK Inhibitors
Leads to reactivation of MAPK signalling pathway

Question 11

Challenges in MANAGEMENT OF

CHECKPOINT INHIBITION THERAPY

Answer 11

Only 40% of patients respond to these therapies.

+ acquired resistance is more probable when treated with a single agent compared to combination (Ctla-4 and PD1/PDL1)

Question 12

Response rate of target therapy vs checkpoint therapy

Answer 12

Target therapy is faster response