FRCR Oncology Part 1: CLINICAL PHARMACOLOGY - 7 (50 QUESTIONS, ANSWERS BELOW)

 

1. Which of the following genetic polymorphisms significantly increases the risk of life-threatening toxicity from irinotecan therapy?
    A. UGT1A128
    B. TPMT3A
    C. DPD2
    D. CYP2D64
    E. ALDH2*2

2. The dose-limiting toxicity of oxaliplatin is due to:
    A. Mitochondrial DNA damage
    B. Calcium channel blockade
    C. DNA intercalation
    D. Sodium channel hyperexcitability
    E. Acetylcholinesterase inhibition

3. Which drug’s anticancer effect depends on inhibition of ribonucleotide reductase?
    A. Hydroxyurea
    B. Methotrexate
    C. Fludarabine
    D. Gemcitabine
    E. Cytarabine

4. Which immunotherapy-related toxicity is most likely to be irreversible even after cessation of therapy?
    A. Hypophysitis
    B. Colitis
    C. Pneumonitis
    D. Thyroiditis
    E. Hepatitis

5. Which of the following agents most selectively inhibits mTORC1 but not mTORC2?
    A. Everolimus
    B. Temsirolimus
    C. Sirolimus
    D. AZD8055
    E. TAK-228

6. The reduced efficacy of cetuximab in KRAS-mutated colorectal cancer is best explained by:
    A. EGFR downregulation
    B. BRAF co-mutation
    C. Constitutive downstream MAPK pathway activation
    D. PI3K hyperactivation
    E. Enhanced ligand recycling

7. Which adverse effect of bevacizumab is mediated via endothelial nitric oxide synthase (eNOS) inhibition?
    A. Gastrointestinal perforation
    B. Hypertension
    C. Proteinuria
    D. Arterial thromboembolism
    E. Hemorrhage

8. Which of the following tyrosine kinase inhibitors also inhibits RET rearrangements in NSCLC?
    A. Vandetanib
    B. Crizotinib
    C. Sunitinib
    D. Lenvatinib
    E. Osimertinib

9. The mechanism of peripheral neuropathy caused by bortezomib involves:
    A. Demyelination of motor neurons
    B. Mitochondrial dysfunction and oxidative stress
    C. Glutamate-mediated excitotoxicity
    D. Inhibition of NMDA receptor recycling
    E. Enhanced microglial activation

10. Which checkpoint blockade leads most commonly to autoimmune diabetes?
     A. PD-1
     B. PD-L1
     C. CTLA-4
     D. LAG-3
     E. TIM-3

11. What is the primary site of action of azacitidine in cancer therapy?
     A. Cytoplasmic ribosome
     B. Nuclear RNA polymerase II
     C. DNA methyltransferase in S-phase
     D. Histone deacetylase in G0
     E. Microtubule spindle checkpoint

12. Which drug causes cardiomyopathy via topoisomerase IIβ inhibition in cardiomyocytes?
     A. Doxorubicin
     B. Trastuzumab
     C. Cyclophosphamide
     D. Daunorubicin
     E. Sorafenib

13. Which TKI has the narrowest therapeutic index and requires therapeutic drug monitoring?
     A. Imatinib
     B. Dasatinib
     C. Nilotinib
     D. Sunitinib
     E. Everolimus

14. Which alkylating agent is metabolised by aldehyde oxidase in the liver to a toxic metabolite causing encephalopathy?
     A. Temozolomide
     B. Ifosfamide
     C. Procarbazine
     D. Lomustine
     E. Busulfan

15. Which anticancer drug must be dose-reduced in patients with Gilbert syndrome?
     A. Capecitabine
     B. Irinotecan
     C. Methotrexate
     D. Paclitaxel
     E. Carboplatin

16. Which immunomodulator used in oncology is associated with VTE and requires prophylactic anticoagulation?
     A. Thalidomide
     B. Bortezomib
     C. Lenalidomide
     D. Interferon-alpha
     E. Panobinostat

17. Which of the following adverse effects of CAR T-cell therapy may be mitigated by IL-6 inhibition?
     A. Neurologic toxicity
     B. Cytokine release syndrome
     C. Graft-versus-host disease
     D. Tumour lysis syndrome
     E. Autoimmune thyroiditis

18. A major mechanism of resistance to anti-EGFR therapy in colorectal cancer is:
     A. KRAS mutation
     B. Increased E-cadherin
     C. PTEN deletion
     D. PD-L1 upregulation
     E. IGF-1 overexpression

19. Which of the following TKIs is most associated with QT prolongation and torsades de pointes?
     A. Lapatinib
     B. Vandetanib
     C. Sorafenib
     D. Crizotinib
     E. Pazopanib

20. The mechanism of action of palbociclib involves:
     A. Inhibition of PI3K
     B. Inhibition of CDK4/6
     C. Inhibition of mTOR
     D. Inhibition of EGFR
     E. Inhibition of JAK/STAT pathway

21. Temozolomide’s anticancer effect is mediated by:
     A. Intercalation into DNA
     B. Inhibition of purine synthesis
     C. Alkylation of O6-guanine
     D. Inhibition of thymidylate synthase
     E. DNA topoisomerase I inhibition

22. Which agent is most likely to cause Fanconi syndrome in long-term use?
     A. Ifosfamide
     B. Cisplatin
     C. Methotrexate
     D. Topotecan
     E. Bleomycin

23. A patient with severe stomatitis and diarrhea on 5-FU likely has a deficiency in:
     A. DPYD
     B. UGT1A1
     C. TPMT
     D. MTHFR
     E. GSTP1

24. Which agent is most likely to cause reactivation of latent tuberculosis?
     A. Bevacizumab
     B. Rituximab
     C. Atezolizumab
     D. Temsirolimus
     E. Nivolumab

25. Which DNA repair enzyme confers resistance to temozolomide when overexpressed?
     A. PARP
     B. MGMT
     C. XRCC1
     D. MSH2
     E. BRCA1

26. Which kinase inhibitor is most selective for ROS1 fusion-positive NSCLC?
     A. Entrectinib
     B. Lenvatinib
     C. Sunitinib
     D. Brigatinib
     E. Afatinib

27. Methotrexate-induced nephrotoxicity is most closely associated with:
     A. Precipitation in acidic urine
     B. Tubular interstitial inflammation
     C. Glomerular sclerosis
     D. Antibody-mediated vasculitis
     E. Complement activation

28. Which drug’s efficacy is enhanced in tumors with BRCA1/2 loss-of-function mutations?
     A. Irinotecan
     B. Cisplatin
     C. Bevacizumab
     D. Palbociclib
     E. Doxorubicin

29. Which agent is most likely to cause irreversible pulmonary fibrosis?
     A. Bleomycin
     B. Gemcitabine
     C. Docetaxel
     D. Vinblastine
     E. Etoposide

30. What is the mechanism of tumor lysis syndrome with venetoclax?
     A. Cytoplasmic calcium overload
     B. Mitochondrial outer membrane permeabilization
     C. Proteasome inhibition
     D. NADPH oxidase activation
     E. Cell cycle arrest at G0/G1

31. Which of the following is NOT a substrate for P-glycoprotein?
     A. Paclitaxel
     B. Vincristine
     C. Doxorubicin
     D. Methotrexate
     E. Imatinib

32. Which pharmacodynamic effect best explains the improved PFS in combination therapy of pembrolizumab and axitinib in RCC?
     A. Antiangiogenic tumor normalization
     B. VEGFR upregulation
     C. Treg cell depletion
     D. Increased MDSC infiltration
     E. Direct cytotoxic synergy

33. What accounts for increased bleeding risk with regorafenib?
     A. Inhibition of platelet-derived growth factor
     B. Reduction in von Willebrand factor
     C. VEGFR2 inhibition
     D. Downregulation of tissue factor
     E. GP IIb/IIIa antagonism

34. Which drug inhibits nuclear export via CRM1 (XPO1)?
     A. Selinexor
     B. Belantamab
     C. Venetoclax
     D. Obinutuzumab
     E. Niraparib

35. Which enzyme is inhibited by vorinostat?
     A. Histone deacetylase
     B. Tyrosine hydroxylase
     C. JAK2
     D. DNA methyltransferase
     E. IDH1

36. What is the mechanism of resistance to PARP inhibitors in ovarian cancer?
     A. BRCA reversion mutations
     B. EGFR overexpression
     C. Increased ABCB1 efflux
     D. PTEN loss
     E. KRAS activation

37. Which agent shows synthetic lethality in mismatch repair-deficient colorectal cancer?
     A. Nivolumab
     B. Temozolomide
     C. Topotecan
     D. Capecitabine
     E. Methotrexate

38. Which TKI has the highest CNS penetration in ALK-positive NSCLC?
     A. Alectinib
     B. Crizotinib
     C. Ceritinib
     D. Lorlatinib
     E. Brigatinib

39. What is the most likely explanation for early-onset severe neutropenia with paclitaxel?
     A. ABCB1 polymorphism
     B. CYP3A5 ultra-rapid metabolizer status
     C. Germline BRCA2 mutation
     D. Bone marrow niche disruption
     E. Reduced expression of microtubule-associated protein

40. Which immunotherapy agent targets both PD-L1 and TGF-β pathways?
     A. Bintrafusp alfa
     B. Atezolizumab
     C. Nivolumab
     D. Durvalumab
     E. Ipilimumab

41. A woman receiving cyclophosphamide develops hemorrhagic cystitis. Which agent prevents this?
     A. Mesna
     B. Leucovorin
     C. Amifostine
     D. N-acetylcysteine
     E. Atropine

42. Which drug used in hematologic malignancies causes dose-dependent ocular toxicity?
     A. Belantamab mafodotin
     B. Venetoclax
     C. Ibrutinib
     D. Obinutuzumab
     E. Asparaginase

43. The function of SLFN11 expression in predicting response to chemotherapy is based on:
     A. DNA replication stress
     B. Immune checkpoint activity
     C. p53-independent apoptosis
     D. ROS generation
     E. EGFR amplification

44. Which of the following is most strongly linked to checkpoint inhibitor-induced myocarditis?
     A. Shared T-cell receptor clonality with skeletal muscle
     B. Anti-dsDNA antibody production
     C. Loss of PD-L2
     D. Upregulation of IL-23
     E. Mast cell activation

45. The antineoplastic action of pralatrexate is due to:
     A. Inhibition of thymidylate synthase
     B. High affinity for reduced folate carrier
     C. Covalent DNA crosslinking
     D. Microtubule disruption
     E. Induction of autophagy

46. Which chemotherapeutic agent's activity depends on S-phase specificity?
     A. Cytarabine
     B. Vincristine
     C. Doxorubicin
     D. Cyclophosphamide
     E. Paclitaxel

47. In CAR T-cell therapy, tonic signaling refers to:
     A. Continuous, antigen-independent activation
     B. Prolonged cytokine release post-activation
     C. Delayed CAR expression
     D. Memory T-cell differentiation
     E. T-cell exhaustion

48. Which PARP inhibitor is least likely to inhibit PARP2?
     A. Niraparib
     B. Rucaparib
     C. Talazoparib
     D. Olaparib
     E. Veliparib

49. Which oral TKI used in thyroid cancer has VEGFR, FGFR, and RET activity?
     A. Lenvatinib
     B. Vandetanib
     C. Pazopanib
     D. Sorafenib
     E. Regorafenib

50. Which chemotherapy agent's neurotoxicity is exacerbated by cold exposure?
     A. Oxaliplatin
     B. Vincristine
     C. Cisplatin
     D. Paclitaxel
     E. Carboplatin

ANSWER

1. A. UGT1A1*28

2. D. Sodium channel hyperexcitability

3. A. Hydroxyurea

4. D. Thyroiditis

5. A. Everolimus

6. C. Constitutive downstream MAPK pathway activation

7. B. Hypertension

8. A. Vandetanib

9. B. Mitochondrial dysfunction and oxidative stress

10. A. PD-1

11. C. DNA methyltransferase in S-phase

12. A. Doxorubicin

13. C. Nilotinib

14. C. Procarbazine

15. B. Irinotecan

16. C. Lenalidomide

17. B. Cytokine release syndrome

18. A. KRAS mutation

19. B. Vandetanib

20. B. Inhibition of CDK4/6

21. C. Alkylation of O6-guanine

22. A. Ifosfamide

23. A. DPYD

24. D. Temsirolimus

25. B. MGMT

26. A. Entrectinib

27. A. Precipitation in acidic urine

28. B. Cisplatin

29. A. Bleomycin

30. B. Mitochondrial outer membrane permeabilization

31. D. Methotrexate

32. A. Antiangiogenic tumor normalization

33. C. VEGFR2 inhibition

34. A. Selinexor

35. A. Histone deacetylase

36. A. BRCA reversion mutations

37. A. Nivolumab

38. D. Lorlatinib

39. A. ABCB1 polymorphism

40. A. Bintrafusp alfa

41. A. Mesna

42. A. Belantamab mafodotin

43. A. DNA replication stress

44. A. Shared T-cell receptor clonality with skeletal muscle

45. B. High affinity for reduced folate carrier

46. A. Cytarabine

47. A. Continuous, antigen-independent activation

48. A. Niraparib

49. A. Lenvatinib

50. A. Oxaliplatin