Question

Tyrosine kinase inhibitors in GIST.

Hint:

TKIs have revolutionized the treatment of GISTs, especially in cases with specific gene mutations, offering improved survival outcomes.

Answer 1

Tyrosine kinase inhibitors (TKIs) are essential in the treatment of gastrointestinal stromal tumors (GISTs), particularly in tumors that have mutations in the KIT or PDGFRA genes.
Step 1: Mechanism of Action of TKIs:
1. Targeting Mutant KIT/PDGFRA Proteins: TKIs work by inhibiting the abnormal tyrosine kinase activity caused by mutations in the KIT or PDGFRA genes, which are commonly found in GISTs.
2. Blocking Cell Proliferation: By inhibiting the tyrosine kinase signaling pathway, TKIs prevent tumor cell proliferation, survival, and metastasis.
Step 2: Commonly Used Tyrosine Kinase Inhibitors:
1. Imatinib (Gleevec): The first-line treatment for advanced GISTs, it has shown significant efficacy in tumors with KIT mutations.
2. Sunitinib (Sutent): An alternative treatment used when tumors become resistant to imatinib.
Step 3: Side Effects of TKIs:
1. Gastrointestinal Symptoms: Nausea, diarrhea, and abdominal discomfort are common side effects.
2. Fatigue and Edema: These are other frequently reported side effects in patients on TKI therapy.