MCQ Quiz: Personalized Medicine in Oncology

Welcome, PharmD students, to this specialized MCQ quiz on Personalized Medicine in Oncology! The treatment of cancer is rapidly evolving towards a more individualized approach, driven by our increasing understanding of tumor biology and the molecular drivers of cancer. Personalized oncology leverages biomarkers, genomic profiling, and an array of targeted therapies and immunotherapies to tailor treatment strategies for better efficacy and reduced toxicity. This quiz will test your knowledge on these critical concepts, from identifying actionable mutations to understanding the role of pharmacogenomics in cancer care. Let’s explore the forefront of cancer treatment!

1. The primary goal of personalized medicine in oncology is to:

• a) Use the same chemotherapy regimen for all patients with a specific cancer type.
• b) Tailor cancer treatment based on the individual molecular characteristics of the patient’s tumor and their germline genetic makeup.
• c) Focus exclusively on palliative care for all cancer patients.
• d) Reduce the cost of all cancer medications.

Answer: b) Tailor cancer treatment based on the individual molecular characteristics of the patient’s tumor and their germline genetic makeup.

2. A “predictive biomarker” in oncology is a measurable characteristic that helps to:

• a) Estimate the patient’s overall prognosis regardless of treatment.
• b) Identify individuals who are more likely to respond to a specific cancer therapy or experience toxicity.
• c) Confirm the initial diagnosis of cancer.
• d) Monitor the patient’s nutritional status.

Answer: b) Identify individuals who are more likely to respond to a specific cancer therapy or experience toxicity.

3. HER2/neu overexpression or amplification is a predictive biomarker for response to which targeted therapy in breast cancer?

• a) Tamoxifen
• b) Trastuzumab (Herceptin)
• c) Bevacizumab (Avastin)
• d) Imatinib (Gleevec)

Answer: b) Trastuzumab (Herceptin)

4. Activating mutations in the EGFR gene in non-small cell lung cancer (NSCLC) are predictive of response to:

• a) Immune checkpoint inhibitors like pembrolizumab.
• b) Traditional cytotoxic chemotherapy like cisplatin.
• c) EGFR tyrosine kinase inhibitors (TKIs) like erlotinib or osimertinib.
• d) Anti-angiogenic agents like bevacizumab.

Answer: c) EGFR tyrosine kinase inhibitors (TKIs) like erlotinib or osimertinib.

5. “Somatic mutations” in cancer are genetic alterations that:

• a) Are inherited from parents and present in all cells of the body.
• b) Occur in the tumor cells themselves and are not typically inherited.
• c) Only affect drug-metabolizing enzymes.
• d) Always lead to drug resistance.

Answer: b) Occur in the tumor cells themselves and are not typically inherited.

6. Imatinib is a tyrosine kinase inhibitor highly effective in chronic myeloid leukemia (CML) due to its specific inhibition of:

• a) HER2
• b) EGFR
• c) BCR-ABL fusion protein
• d) VEGF receptor

Answer: c) BCR-ABL fusion protein

7. Testing for KRAS mutations is important before initiating anti-EGFR monoclonal antibody therapy (e.g., cetuximab, panitumumab) in colorectal cancer because:

• a) KRAS mutations predict a favorable response to these agents.
• b) The presence of certain KRAS mutations predicts a lack of response (resistance) to these agents.
• c) All colorectal cancer patients have KRAS mutations.
• d) KRAS mutations increase the metabolism of these antibodies.

Answer: b) The presence of certain KRAS mutations predicts a lack of response (resistance) to these agents.

8. PD-L1 expression on tumor cells or immune cells is a biomarker sometimes used to predict response to which class of anticancer drugs?

• a) Alkylating agents
• b) Antimetabolites
• c) Immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies)
• d) Aromatase inhibitors

Answer: c) Immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies)

9. Germline mutations in DPYD, the gene encoding dihydropyrimidine dehydrogenase, can lead to severe toxicity with which chemotherapeutic agent?

• a) Methotrexate
• b) 5-Fluorouracil (and its prodrug capecitabine)
• c) Cisplatin
• d) Doxorubicin

Answer: b) 5-Fluorouracil (and its prodrug capecitabine)

10. UGT1A1 gene polymorphisms, particularly the UGT1A1*28 allele, are associated with an increased risk of severe neutropenia and diarrhea with which anticancer drug?

• a) Paclitaxel
• b) Vincristine
• c) Irinotecan (due to impaired metabolism of its active metabolite SN-38)
• d) Bleomycin

Answer: c) Irinotecan (due to impaired metabolism of its active metabolite SN-38)

11. Next-Generation Sequencing (NGS) is a technology frequently used in personalized oncology for:

• a) Only measuring patient height and weight.
• b) Simultaneously analyzing multiple genes or entire tumor genomes/exomes for relevant mutations, amplifications, or translocations.
• c) Administering radiation therapy.
• d) Performing surgical procedures.

Answer: b) Simultaneously analyzing multiple genes or entire tumor genomes/exomes for relevant mutations, amplifications, or translocations.

12. A “liquid biopsy” in oncology typically involves analyzing _______ for tumor-derived material like circulating tumor DNA (ctDNA).

• a) A solid tumor tissue sample
• b) A blood sample (or other body fluids)
• c) Bone marrow aspirate only
• d) Saliva only

Answer: b) A blood sample (or other body fluids)

13. The concept of “oncogene addiction” suggests that some cancer cells are highly dependent on a single activated oncogenic pathway for survival and proliferation. This provides a rationale for:

• a) Using non-specific cytotoxic chemotherapy.
• b) Developing targeted therapies that inhibit that specific oncogenic pathway.
• c) Only using radiation therapy.
• d) Palliative care as the only option.

Answer: b) Developing targeted therapies that inhibit that specific oncogenic pathway.

14. BRAF V600E mutation is a common target in which cancer type, treatable with BRAF inhibitors (e.g., vemurafenib, dabrafenib)?

• a) Chronic myeloid leukemia
• b) ER-positive breast cancer
• c) Melanoma
• d) Small cell lung cancer

Answer: c) Melanoma

15. Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficiency (dMMR) status in tumors is a predictive biomarker for favorable response to which class of therapy across multiple cancer types?

• a) Hormonal therapy
• b) Immune checkpoint inhibitors (e.g., pembrolizumab)
• c) Alkylating agents
• d) Antimetabolites

Answer: b) Immune checkpoint inhibitors (e.g., pembrolizumab)

16. One of the major challenges in personalized oncology with targeted therapies is the development of:

• a) Universal efficacy in all patients.
• b) Acquired resistance mechanisms by the tumor cells.
• c) Complete lack of side effects.
• d) Reduced cost of treatment over time.

Answer: b) Acquired resistance mechanisms by the tumor cells.

17. An “actionable mutation” in cancer genomics is a genetic alteration for which:

• a) There is no known clinical significance.
• b) A specific targeted therapy exists that can improve patient outcomes, or it has prognostic/diagnostic implications.
• c) It is found in all healthy individuals.
• d) It guarantees a cure with any treatment.

Answer: b) A specific targeted therapy exists that can improve patient outcomes, or it has prognostic/diagnostic implications.

18. The pharmacology of many small molecule tyrosine kinase inhibitors (TKIs) involves competitive binding at the _______ site of the target kinase.

• a) Allosteric regulatory
• b) DNA-binding
• c) ATP-binding
• d) Ligand-binding (for receptor TKs)

Answer: c) ATP-binding

19. Antibody-drug conjugates (ADCs) represent a personalized approach by linking a potent cytotoxic drug to a monoclonal antibody that targets a specific antigen on cancer cells. The goal is to:

• a) Increase systemic toxicity.
• b) Deliver the cytotoxic payload preferentially to cancer cells, minimizing exposure to normal cells.
• c) Enhance the immunogenicity of the antibody.
• d) Only stimulate the immune system.

Answer: b) Deliver the cytotoxic payload preferentially to cancer cells, minimizing exposure to normal cells.

20. Germline pharmacogenomic testing in oncology (e.g., for DPYD, UGT1A1, TPMT) helps to predict potential for _______ with certain chemotherapy drugs.

• a) Enhanced efficacy only
• b) Drug-induced toxicities due to altered drug metabolism or disposition
• c) Tumor-specific mutations
• d) Resistance to targeted therapies

Answer: b) Drug-induced toxicities due to altered drug metabolism or disposition

21. What is a primary advantage of using liquid biopsies (e.g., ctDNA analysis) in personalized oncology?

• a) They are always more accurate than tissue biopsies for initial diagnosis.
• b) They are less invasive than tissue biopsies and can be used for monitoring tumor evolution and response to therapy over time.
• c) They only detect germline mutations.
• d) They are not affected by tumor heterogeneity.

Answer: b) They are less invasive than tissue biopsies and can be used for monitoring tumor evolution and response to therapy over time.

22. Tumor heterogeneity, both inter-tumoral (between patients) and intra-tumoral (within a single patient’s tumor), poses a challenge for personalized medicine because:

• a) It makes all tumors respond identically to treatment.
• b) A therapy targeting a specific alteration found in only a subclone of cancer cells may not be effective against the entire tumor or may lead to resistance.
• c) It simplifies biomarker testing.
• d) It ensures targeted therapies are always curative.

Answer: b) A therapy targeting a specific alteration found in only a subclone of cancer cells may not be effective against the entire tumor or may lead to resistance.

23. The FDA often approves targeted oncology drugs concomitantly with a specific _______ to identify patients eligible for treatment.

• a) Antiemetic regimen
• b) Companion diagnostic test
• c) Surgical procedure
• d) Palliative care plan

Answer: b) Companion diagnostic test

24. ALK gene rearrangements (e.g., EML4-ALK fusion) in non-small cell lung cancer are treated with targeted therapies like:

• a) EGFR inhibitors (e.g., erlotinib)
• b) ALK inhibitors (e.g., crizotinib, alectinib)
• c) BRAF inhibitors (e.g., vemurafenib)
• d) Immune checkpoint inhibitors

Answer: b) ALK inhibitors (e.g., crizotinib, alectinib)

25. Which statement best describes the role of “tumor mutational burden” (TMB) as a biomarker in oncology?

• a) A low TMB always predicts good response to chemotherapy.
• b) A high TMB (many mutations) may predict better response to immune checkpoint inhibitors in some cancers, as it can generate more neoantigens.
• c) TMB is only relevant for hormonal therapies.
• d) TMB is a measure of tumor size.

Answer: b) A high TMB (many mutations) may predict better response to immune checkpoint inhibitors in some cancers, as it can generate more neoantigens.

26. The medicinal chemistry of targeted kinase inhibitors often involves designing molecules with high affinity and selectivity for the target kinase to:

• a) Increase off-target toxicities.
• b) Maximize on-target efficacy and minimize off-target side effects.
• c) Ensure the drug binds to all kinases in the cell.
• d) Make the drug more water-soluble only.

Answer: b) Maximize on-target efficacy and minimize off-target side effects.

27. Which of the following is an example of a pharmacodynamic biomarker in oncology?

• a) A germline SNP in a CYP450 enzyme.
• b) Measurement of target inhibition (e.g., phosphorylated downstream protein) in tumor tissue after drug administration.
• c) The patient’s age.
• d) The total dose of chemotherapy administered.

Answer: b) Measurement of target inhibition (e.g., phosphorylated downstream protein) in tumor tissue after drug administration.

28. Resistance to EGFR inhibitors like gefitinib or erlotinib in NSCLC can occur through secondary mutations in the EGFR gene, such as:

• a) BRAF V600E
• b) T790M mutation
• c) BCR-ABL translocation
• d) KRAS G12C

Answer: b) T790M mutation (Osimertinib was developed to overcome this).

29. The principle of synthetic lethality is a personalized oncology approach where:

• a) Two non-toxic drugs are combined to create a highly toxic effect on all cells.
• b) A drug targets a pathway that is essential for cancer cell survival only when another specific gene (often a tumor suppressor) is mutated or lost.
• c) All cancer cells are killed synthetically.
• d) The immune system is synthetically enhanced.

Answer: b) A drug targets a pathway that is essential for cancer cell survival only when another specific gene (often a tumor suppressor) is mutated or lost. (e.g., PARP inhibitors in BRCA-mutated cancers).

30. Osimertinib, a third-generation EGFR TKI, was specifically designed from a medicinal chemistry perspective to be effective against NSCLC with:

• a) Only wild-type EGFR.
• b) Both sensitizing EGFR mutations and the T790M resistance mutation, while sparing wild-type EGFR to a greater extent.
• c) ALK rearrangements.
• d) KRAS mutations.

Answer: b) Both sensitizing EGFR mutations and the T790M resistance mutation, while sparing wild-type EGFR to a greater extent.

31. The use of patient-derived xenografts (PDX models) in personalized oncology research involves:

• a) Testing drugs on standard cancer cell lines only.
• b) Implanting a patient’s tumor tissue into immunodeficient mice to test drug responses in a more individualized preclinical model.
• c) Computer simulations of drug effects.
• d) Analyzing a patient’s blood for biomarkers.

Answer: b) Implanting a patient’s tumor tissue into immunodeficient mice to test drug responses in a more individualized preclinical model.

32. Ethical considerations in personalized oncology include:

• a) Ensuring that benefits of targeted therapies outweigh the financial burden on patients.
• b) Management of incidental germline findings from tumor sequencing.
• c) Equitable access to genomic testing and targeted drugs.
• d) All of the above.

Answer: d) All of the above.

33. The “basket trial” design in oncology clinical trials for personalized medicine tests:

• a) A single drug in patients with many different types of cancer that all share the same specific molecular alteration targeted by the drug.
• b) Many different drugs in patients with only one type of cancer.
• c) Only traditional chemotherapy regimens.
• d) The effect of different basket types on fruit preservation.

Answer: a) A single drug in patients with many different types of cancer that all share the same specific molecular alteration targeted by the drug.

34. “Umbrella trials” in personalized oncology test:

• a) A single drug across many cancer types.
• b) Multiple different targeted therapies in patients with a single cancer type, where patients are assigned to a therapy based on their specific tumor molecular alterations.
• c) Only the effectiveness of different types of umbrellas in rainy weather.
• d) Only palliative care strategies.

Answer: b) Multiple different targeted therapies in patients with a single cancer type, where patients are assigned to a therapy based on their specific tumor molecular alterations.

35. The pharmacogenomic implications of TPMT polymorphisms for thiopurine drugs (e.g., 6-mercaptopurine in leukemia) are critical because individuals with low/deficient TPMT activity:

• a) Will have enhanced efficacy with standard doses.
• b) Are at high risk of severe hematologic toxicity if given standard doses due to accumulation of active thioguanine nucleotides.
• c) Require higher doses of thiopurines.
• d) Will not respond to thiopurines at all.

Answer: b) Are at high risk of severe hematologic toxicity if given standard doses due to accumulation of active thioguanine nucleotides.

36. One of the primary challenges in the clinical implementation of “OMICS” data (genomics, proteomics, etc.) for personalized oncology is:

• a) The simplicity of the data.
• b) The lack of any identified biomarkers.
• c) The interpretation of the vast amounts of complex data into clinically actionable information and integrating it into decision-making.
• d) The universal effectiveness of a single targeted drug for all mutations.

Answer: c) The interpretation of the vast amounts of complex data into clinically actionable information and integrating it into decision-making.

37. The development of resistance to immune checkpoint inhibitors can occur through mechanisms such as:

• a) Increased PD-L1 expression on tumor cells.
• b) Loss of antigen presentation machinery (e.g., MHC class I) by tumor cells or alterations in interferon signaling.
• c) Enhanced T-cell activation.
• d) Decreased tumor mutational burden.

Answer: b) Loss of antigen presentation machinery (e.g., MHC class I) by tumor cells or alterations in interferon signaling.

38. A key principle when discussing personalized medicine with cancer patients is to:

• a) Guarantee a cure if a targeted therapy is available.
• b) Manage expectations, explaining that while it aims to improve outcomes, it’s not always curative and resistance can develop.
• c) Avoid discussing any potential side effects of targeted therapies.
• d) Tell them genetic testing is infallible.

Answer: b) Manage expectations, explaining that while it aims to improve outcomes, it’s not always curative and resistance can develop.

39. The concept of “driver mutations” in cancer refers to genetic alterations that:

• a) Are random and have no impact on cancer development.
• b) Confer a growth or survival advantage to cancer cells and are critical for tumor initiation or progression.
• c) Are only found in normal, healthy cells.
• d) Make cancer cells more susceptible to apoptosis.

Answer: b) Confer a growth or survival advantage to cancer cells and are critical for tumor initiation or progression.

40. Pharmacists in personalized oncology play a role in interpreting and applying results from which type of tests to optimize drug therapy?

• a) Only routine blood chemistry panels.
• b) Tumor genomic profiling and germline pharmacogenomic tests.
• c) Only allergy skin tests.
• d) Only visual acuity tests.

Answer: b) Tumor genomic profiling and germline pharmacogenomic tests.

41. The field of radiogenomics in personalized oncology aims to correlate:

• a) Radiographic imaging features with genomic characteristics of tumors to predict treatment response or prognosis.
• b) The patient’s radiation exposure from X-rays with their hair color.
• c) The radioactivity of drugs with their efficacy.
• d) Only the dose of radiation therapy.

Answer: a) Radiographic imaging features with genomic characteristics of tumors to predict treatment response or prognosis.

42. Which of the following is a challenge related to tumor biopsies for personalized medicine?

• a) They are always non-invasive.
• b) A single biopsy may not capture the full extent of intra-tumor heterogeneity.
• c) They always provide enough DNA for any type of genomic analysis.
• d) They are inexpensive and readily available everywhere.

Answer: b) A single biopsy may not capture the full extent of intra-tumor heterogeneity.

43. The use of “molecular tumor boards” in personalized oncology involves:

• a) Patients discussing their tumor experiences.
• b) A multidisciplinary team of experts (oncologists, pathologists, geneticists, bioinformaticians, pharmacists) reviewing complex genomic data to recommend personalized treatment strategies.
• c) Surgeons only, discussing operative techniques.
• d) Pharmaceutical company representatives marketing new drugs.

Answer: b) A multidisciplinary team of experts (oncologists, pathologists, geneticists, bioinformaticians, pharmacists) reviewing complex genomic data to recommend personalized treatment strategies.

44. Understanding the specific signaling pathways dysregulated in a patient’s cancer (e.g., PI3K/AKT/mTOR pathway) is a core principle for selecting appropriate:

• a) Broad-spectrum cytotoxic chemotherapy.
• b) Targeted therapies that inhibit components of that specific pathway.
• c) Hormonal therapies for all cancer types.
• d) Radiotherapy sensitizers.

Answer: b) Targeted therapies that inhibit components of that specific pathway.

45. “Clonal evolution” of tumors is a major factor contributing to:

• a) The initial diagnosis of cancer.
• b) The development of therapeutic resistance and disease progression in personalized oncology.
• c) The consistent sensitivity of all cancer cells to a single drug.
• d) The benign nature of most tumors.

Answer: b) The development of therapeutic resistance and disease progression in personalized oncology.

46. The medicinal chemistry of antibody-drug conjugates (ADCs) involves careful design of the antibody, the cytotoxic payload, and the _______, which influences stability and payload release.

• a) patient’s diet
• b) linker
• c) color of the drug
• d) container closure system

Answer: b) linker

47. For personalized oncology to be effective, there’s a need for robust clinical trials that incorporate _______ to identify patient subgroups who benefit most.

• a) only elderly male subjects
• b) integral biomarker strategies
• c) no control groups
• d) only subjective patient reports

Answer: b) integral biomarker strategies

48. A key difference between pharmacogenomic testing of germline DNA versus somatic (tumor) DNA in oncology is that:

• a) Germline DNA testing guides therapy targeting inherited variations affecting drug ADME or sensitivity, while somatic DNA testing identifies tumor-specific mutations for targeted therapy.
• b) Somatic DNA testing is only for predicting side effects.
• c) Germline DNA testing is only for diagnosing cancer.
• d) There is no difference; they provide the same information.

Answer: a) Germline DNA testing guides therapy targeting inherited variations affecting drug ADME or sensitivity, while somatic DNA testing identifies tumor-specific mutations for targeted therapy.

49. The success of immunotherapies like checkpoint inhibitors in some patients has highlighted the importance of _______ in personalized cancer treatment.

• a) completely suppressing the immune system
• b) understanding and leveraging the tumor microenvironment and host immune status
• c) using only chemotherapy
• d) ignoring biomarkers

Answer: b) understanding and leveraging the tumor microenvironment and host immune status

50. The future of personalized medicine in oncology likely involves:

• a) A return to one-size-fits-all treatment approaches.
• b) Integration of multi-omics data (genomics, transcriptomics, proteomics, metabolomics), advanced bioinformatics, artificial intelligence, and novel therapeutic strategies.
• c) Using fewer diagnostic tests.
• d) Focusing only on surgical interventions.

Answer: b) Integration of multi-omics data (genomics, transcriptomics, proteomics, metabolomics), advanced bioinformatics, artificial intelligence, and novel therapeutic strategies.