FRCR Oncology Part 1: CLINICAL PHARMACOLOGY - 8 (50 QUESTIONS, ANSWERS BELOW)

 

1. Which metabolite is primarily responsible for ifosfamide-induced neurotoxicity?
    A. Acrolein
    B. Chloroacetaldehyde
    C. 4-hydroxy-ifosfamide
    D. Carboxyifosfamide
    E. Norifosfamide

2. Which immunotherapy-related adverse event is associated with anti-CTLA-4 more than anti-PD-1 agents?
    A. Pneumonitis
    B. Hypophysitis
    C. Hepatitis
    D. Nephritis
    E. Neuropathy

3. Which transporter mediates methotrexate uptake into cells?
    A. P-glycoprotein
    B. OATP1B1
    C. Reduced folate carrier (RFC1)
    D. MATE1
    E. OAT3

4. Which genetic mutation leads to resistance to BRAF inhibitors in melanoma?
    A. PTEN loss
    B. MEK1 mutation
    C. EGFR overexpression
    D. KRAS amplification
    E. c-MET fusion

5. Which alkylating agent produces interstrand crosslinks at N7 of guanine and is not cell-cycle specific?
    A. Temozolomide
    B. Busulfan
    C. Cisplatin
    D. Cyclophosphamide
    E. Melphalan

6. What best explains the enhanced efficacy of combining radiotherapy with pembrolizumab?
    A. Increased radiosensitivity of tumor vasculature
    B. Upregulation of PD-L1 via IFN-γ
    C. Enhanced Treg recruitment
    D. Depletion of M2 macrophages
    E. Increased DNA repair inhibition

7. What pharmacologic feature of sunitinib contributes to its long duration of action?
    A. High plasma protein binding
    B. Active metabolite with similar potency
    C. Irreversible receptor binding
    D. Renal accumulation
    E. Long terminal half-life

8. Which of the following drugs inhibits aminopeptidase and is used in multiple myeloma?
    A. Carfilzomib
    B. Ixazomib
    C. Belantamab mafodotin
    D. Melflufen
    E. Panobinostat

9. What is the most likely mechanism for immune escape in JAK1-mutated tumors treated with PD-1 inhibitors?
    A. Increased Treg expression
    B. Reduced IFN-γ signaling
    C. PD-L1 gene amplification
    D. MHC class I downregulation
    E. CTLA-4 mutation

10. Which drug induces "mitotic catastrophe" via inhibition of Aurora B kinase?
     A. Alisertib
     B. Palbociclib
     C. Olaparib
     D. Cabazitaxel
     E. Abemaciclib

11. What is the primary mechanism of resistance to CDK4/6 inhibitors in HR+ breast cancer?
     A. RB1 loss
     B. ESR1 mutation
     C. HER2 overexpression
     D. PI3K inhibition
     E. BRCA2 inactivation

12. Which of the following anti-androgens acts as an androgen receptor signaling inhibitor without nuclear translocation?
     A. Bicalutamide
     B. Enzalutamide
     C. Apalutamide
     D. Darolutamide
     E. Flutamide

13. What effect does histone acetylation have on gene expression?
     A. Gene silencing
     B. Chromatin condensation
     C. Transcriptional activation
     D. DNA methylation
     E. Inhibition of replication

14. What is the significance of the drug–drug interaction between tamoxifen and SSRIs like paroxetine?
     A. Increased thromboembolic risk
     B. Reduced CYP2D6 activity
     C. QT prolongation
     D. Increased bone loss
     E. Reduced estrogen receptor expression

15. Which of the following is a mitochondrial apoptosis activator?
     A. Navitoclax
     B. Sorafenib
     C. Obinutuzumab
     D. Crizotinib
     E. Niraparib

16. Which phase of the cell cycle does bleomycin exert its strongest cytotoxic effect?
     A. G0
     B. G1
     C. S
     D. G2
     E. M

17. Which metabolic enzyme is upregulated in hypoxic tumor microenvironments and contributes to drug resistance?
     A. CYP3A4
     B. Aldehyde dehydrogenase
     C. GSTP1
     D. FMO3
     E. UGT2B7

18. Which of the following immune checkpoint inhibitors is associated with highest incidence of colitis?
     A. Ipilimumab
     B. Atezolizumab
     C. Nivolumab
     D. Durvalumab
     E. Cemiplimab

19. Which metabolic pathway does decitabine inhibit?
     A. Purine synthesis
     B. Pyrimidine salvage
     C. DNA methylation
     D. Histone demethylation
     E. RNA polymerase

20. What is the most common resistance mechanism to 5-FU?
     A. Overexpression of thymidylate synthase
     B. DPD deficiency
     C. MMR deficiency
     D. EGFR mutation
     E. BRCA1 loss

21. Which of the following drugs can trigger autoimmune diabetes?
     A. Pembrolizumab
     B. Atezolizumab
     C. Cetuximab
     D. Sorafenib
     E. Sunitinib

22. Which kinase is specifically inhibited by tazemetostat?
     A. EZH2
     B. CDK9
     C. Aurora A
     D. BTK
     E. BRAF

23. Which agent is known to cause capillary leak syndrome?
     A. Aldesleukin
     B. Cetuximab
     C. Palbociclib
     D. Crizotinib
     E. Olaparib

24. The therapeutic efficacy of belantamab mafodotin depends on:
     A. CD38 expression
     B. Antibody-drug conjugate internalization
     C. Fcγ receptor binding
     D. Proteasome inhibition
     E. BTK inhibition

25. Which drug is most associated with "on-target, off-tumor" toxicity?
     A. CAR T-cells targeting HER2
     B. PD-L1 inhibitors
     C. Enzalutamide
     D. Cetuximab
     E. Regorafenib

26. Which resistance mechanism to osimertinib is most commonly acquired in NSCLC?
     A. MET amplification
     B. T790M mutation
     C. ALK translocation
     D. EGFR L861Q
     E. RAS amplification

27. What is the mechanism of pemigatinib?
     A. FGFR inhibitor
     B. RET kinase inhibitor
     C. IDH1 inhibitor
     D. ALK inhibitor
     E. FLT3 inhibitor

28. Which DNA repair pathway is primarily targeted by PARP inhibitors?
     A. Homologous recombination
     B. Non-homologous end joining
     C. Base excision repair
     D. Mismatch repair
     E. Nucleotide excision repair

29. Which factor predicts severe toxicity from irinotecan?
     A. UGT1A1*28 polymorphism
     B. CYP2D6 deficiency
     C. DPD mutation
     D. BCRP overexpression
     E. ALDH1A1 mutation

30. Which monoclonal antibody targets Trop-2 in metastatic breast cancer?
     A. Trastuzumab deruxtecan
     B. Sacituzumab govitecan
     C. Ramucirumab
     D. Brentuximab vedotin
     E. Gemtuzumab ozogamicin

31. The development of cardiomyopathy with trastuzumab is most closely associated with:
     A. Cumulative anthracycline exposure
     B. HER2 mutation
     C. Prior chest irradiation
     D. Low BMI
     E. Diabetes mellitus

32. Which agent is most likely to cause hemolytic uremic syndrome (HUS)?
     A. Gemcitabine
     B. Pemetrexed
     C. Nivolumab
     D. Docetaxel
     E. Imatinib

33. What type of binding does palbociclib exhibit toward CDK4/6?
     A. Competitive reversible
     B. Non-competitive reversible
     C. Irreversible covalent
     D. Allosteric inhibition
     E. Uncompetitive inhibition

34. What best describes the role of SLFN11 in chemotherapy?
     A. Enhancer of DNA damage response
     B. Predictor of resistance to alkylating agents
     C. Inducer of DNA repair suppression
     D. Biomarker of immunotherapy failure
     E. Inhibitor of topoisomerase II

35. What mechanism allows AML cells to evade venetoclax-induced apoptosis?
     A. MCL-1 overexpression
     B. BAX mutation
     C. FLT3-TKD mutation
     D. P-glycoprotein upregulation
     E. TP53 overexpression

36. Which agent is associated with a "cytokine storm" in patients with high tumor burden?
     A. Blinatumomab
     B. Rituximab
     C. Sorafenib
     D. Gefitinib
     E. Everolimus

37. What is the main toxicity limiting dose escalation of alpelisib?
     A. Hyperglycemia
     B. Neutropenia
     C. Rash
     D. Diarrhea
     E. Hepatitis

38. Which fusion protein is targeted by larotrectinib?
     A. NTRK
     B. ALK
     C. ROS1
     D. RET
     E. BCR-ABL

39. The activity of bevacizumab is most dependent on which tumor property?
     A. VEGF expression
     B. Tumor microvessel density
     C. PD-L1 level
     D. Hypoxia-inducible factor-1
     E. Immune cell infiltration

40. Which adverse event is considered a class effect of PI3K inhibitors?
     A. Hyperglycemia
     B. Pneumonitis
     C. QTc prolongation
     D. Cardiotoxicity
     E. Retinopathy

41. Which agent acts as a hypomethylating agent and is incorporated into RNA and DNA?
     A. Azacitidine
     B. Decitabine
     C. Cytarabine
     D. Idarubicin
     E. Nelarabine

42. Which drug targets the CD47 "don't eat me" signal?
     A. Magrolimab
     B. Tagraxofusp
     C. Camidanlumab
     D. Loncastuximab
     E. Polatuzumab

43. What is the principal pharmacokinetic limitation of paclitaxel?
     A. Poor aqueous solubility
     B. Renal clearance
     C. Narrow therapeutic index
     D. Fast hepatic metabolism
     E. P-glycoprotein activation

44. What is the function of MDM2 inhibitors in oncology?
     A. Reactivate p53 tumor suppressor
     B. Inhibit EGFR dimerization
     C. Block DNA methylation
     D. Suppress PI3K/AKT signaling
     E. Enhance histone acetylation

45. Which checkpoint molecule is highly expressed in T-regulatory cells and suppresses anti-tumor immunity?
     A. CTLA-4
     B. OX40
     C. LAG-3
     D. TIM-3
     E. 4-1BB

46. Which drug directly inhibits NEDD8-activating enzyme?
     A. Pevonedistat
     B. Ricolinostat
     C. Venetoclax
     D. Selinexor
     E. Tazemetostat

47. What describes the mechanism of action of selpercatinib?
     A. RET kinase inhibitor
     B. ALK/MET dual inhibitor
     C. CDK4/6 inhibitor
     D. PARP inhibitor
     E. VEGF blocker

48. Which is the primary cellular target of panobinostat?
     A. Histone deacetylase
     B. Topoisomerase I
     C. Aurora kinase B
     D. HDM2
     E. EZH2

49. Which adverse effect is more common with immune checkpoint inhibitor retreatment?
     A. Colitis
     B. Hypothyroidism
     C. Rash
     D. Pneumonitis
     E. Arthralgia

50. What is the rationale for combining BRAF and MEK inhibitors in melanoma?
     A. Prevent paradoxical MAPK pathway activation
     B. Reduce cardiotoxicity
     C. Minimize resistance via AKT
     D. Enhance immune activation
     E. Increase blood–brain barrier penetration

ANSWER

1. B. Chloroacetaldehyde

2. B. Hypophysitis

3. C. Reduced folate carrier (RFC1)

4. B. MEK1 mutation

5. C. Cisplatin

6. B. Upregulation of PD-L1 via IFN-γ

7. E. Long terminal half-life

8. D. Melflufen

9. B. Reduced IFN-γ signaling

10. A. Alisertib

11. A. RB1 loss

12. B. Enzalutamide

13. C. Transcriptional activation

14. B. Reduced CYP2D6 activity

15. A. Navitoclax

16. D. G2

17. C. GSTP1

18. A. Ipilimumab

19. C. DNA methylation

20. A. Overexpression of thymidylate synthase

21. A. Pembrolizumab

22. A. EZH2

23. A. Aldesleukin

24. B. Antibody-drug conjugate internalization

25. A. CAR T-cells targeting HER2

26. A. MET amplification

27. A. FGFR inhibitor

28. A. Homologous recombination

29. A. UGT1A1*28 polymorphism

30. B. Sacituzumab govitecan

31. A. Cumulative anthracycline exposure

32. A. Gemcitabine

33. A. Competitive reversible

34. C. Inducer of DNA repair suppression

35. A. MCL-1 overexpression

36. A. Blinatumomab

37. A. Hyperglycemia

38. A. NTRK

39. B. Tumor microvessel density

40. A. Hyperglycemia

41. A. Azacitidine

42. A. Magrolimab

43. A. Poor aqueous solubility

44. A. Reactivate p53 tumor suppressor

45. A. CTLA-4

46. A. Pevonedistat

47. A. RET kinase inhibitor

48. A. Histone deacetylase

49. A. Colitis

50. A. Prevent paradoxical MAPK pathway activation