AOCNP Cancer Pharmacology and Chemotherapy 2 — Questions and Answers
Question 1: Which targeted therapy is a monoclonal antibody that blocks the HER2 receptor in HER2-positive breast cancer?
- Trastuzumab (Correct answer)
- Erlotinib
- Imatinib
- Bevacizumab
Correct answer: Trastuzumab
Trastuzumab (Herceptin) binds the extracellular domain of HER2, inhibiting downstream proliferative signaling and mediating antibody-dependent cytotoxicity.
Question 2: Imatinib (Gleevec) revolutionized the treatment of CML by targeting:
- The BCR-ABL tyrosine kinase (Correct answer)
- VEGF receptor
- EGFR receptor
- CD20 antigen
Correct answer: The BCR-ABL tyrosine kinase
Imatinib occupies the ATP-binding site of the BCR-ABL fusion kinase, constitutively produced by the Philadelphia chromosome translocation t(9;22).
Question 3: Which toxicity is most uniquely associated with bleomycin that limits its cumulative dosing?
- Pulmonary fibrosis (Correct answer)
- Nephrotoxicity
- Cardiotoxicity
- Hepatotoxicity
Correct answer: Pulmonary fibrosis
Bleomycin accumulates in lung tissue where the inactivating enzyme bleomycin hydrolase is deficient, leading to dose-dependent pulmonary fibrosis.
Question 4: VEGF inhibitor bevacizumab carries which unique risk compared to cytotoxic chemotherapy?
- Arterial thromboembolic events, wound healing impairment, and GI perforation (Correct answer)
- Febrile neutropenia
- Alopecia
- Mucositis
Correct answer: Arterial thromboembolic events, wound healing impairment, and GI perforation
Anti-VEGF therapy impairs angiogenesis needed for wound healing and vascular integrity, increasing risks of arterial thromboembolism, delayed healing, and GI perforation.
Question 5: PARP inhibitors such as olaparib are most effective in tumors with defects in which repair pathway?
- Homologous recombination (BRCA1/2 mutations) (Correct answer)
- Nucleotide excision repair
- Mismatch repair
- Base excision repair only
Correct answer: Homologous recombination (BRCA1/2 mutations)
BRCA1/2-mutated tumors rely solely on PARP-mediated base excision repair; olaparib blocks PARP, causing lethal synthetic lethality in HR-deficient cells.
Question 6: Checkpoint inhibitors targeting PD-1 (e.g., pembrolizumab) cause a distinctive class of toxicities called:
- Immune-related adverse events (irAEs) (Correct answer)
- Infusion-related reactions only
- Cytokine release syndrome
- Tumor lysis syndrome
Correct answer: Immune-related adverse events (irAEs)
By unleashing T-cell activity, PD-1 inhibitors can cause immune-related adverse events across any organ, including colitis, pneumonitis, hepatitis, and endocrinopathies.
AOCNP Cancer Pharmacology and Chemotherapy 2
Which targeted therapy is a monoclonal antibody that blocks the HER2 receptor in HER2-positive breast cancer?