A 58-year-old man with small cell lung carcinoma develops hyponatremia and elevated urine osmolality. Ectopic hormone production by the tumor is responsible. Which gene product directly mediates resistance to apoptosis in this neuroendocrine malignancy, making it particularly refractory to therapy despite initial chemosensitivity?
- A BCL-2 protein
- B Survivin (BIRC5) ✓
- C MDM2 amplification
- D XIAP overexpression
Correct answer: B. Survivin (BIRC5)
Explanation
Survivin (BIRC5), a member of the inhibitor of apoptosis (IAP) family, is highly overexpressed in small cell lung carcinoma and plays a central role in resistance to apoptosis after initial chemosensitivity. Survivin inhibits caspase-3 and caspase-9 and also regulates mitosis as part of the chromosomal passenger complex. BCL-2 is relevant in follicular lymphoma; MDM2 amplification abrogates p53 in well-differentiated liposarcomas; XIAP is broadly expressed but not the primary resistance driver in SCLC.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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