Anticancer Drugs Practice Questions

Q: A 55-year-old male patient complains of an abnormal growth on his right cheek. The patient has a habit of tobacco chewing for 30 years. Radiologic findings reveal an 8x8 cm fungating mass invading the maxilla and mandible on the right side. The patient was advised palliative chemotherapy with cisplatin. Which of the following changes in DNA is NOT caused by this drug?

The changed structure cannot bind proteins. **Explanation:** **Cisplatin** is a platinum-based alkylating-like agent used extensively in ENT oncology for squamous cell carcinomas. Its mechanism of action involves the formation of **intra-strand cross-links** (primarily between adjacent Guanine bases). **Why Option D is Correct:** The core concept is that Cisplatin-induced DNA damage **does not prevent protein binding**; instead, it facilitates the binding of specific proteins. When Cisplatin creates DNA adducts, it causes significant structural distortion (bending). This distorted DNA is specifically recognized and bound by **High Mobility Group (HMG) domain proteins** and other DNA-repair proteins. These proteins "shield" the DNA from repair mechanisms, ultimately leading to programmed cell death (apoptosis). Therefore, saying the structure *cannot* bind proteins is factually incorrect. **Analysis of Incorrect Options:** * **Option A & B:** Cisplatin has a high affinity for specific sequences. It targets G-rich areas and can lead to the disruption of **A-tracts** (sequences of adenine). The resulting cross-links cause a structural **collapse of the DNA helix** into the minor groove, particularly affecting the geometry of A-tracts. * **Option C:** The hallmark of Cisplatin action is the **bending of the DNA duplex** (approximately 30-90 degrees). This bending is essential for its cytotoxic effect as it signals the cell's apoptotic machinery. **Clinical Pearls for NEET-PG:** * **Dose-limiting toxicity:** Nephrotoxicity (prevented by aggressive hydration and Amifostine). * **Other toxicities:** Ototoxicity (high-frequency hearing loss), peripheral neuropathy, and severe emesis (highly emetogenic). * **Mechanism:** Forms **1,2-intrastrand cross-links** (most common) rather than interstrand links.

Q: Which of the following drugs acts by inhibiting the tyrosine kinase activated by the EGF receptor as well as HER2?

Lapatinib. ### Explanation **Correct Option: D. Lapatinib** Lapatinib is a **dual tyrosine kinase inhibitor (TKI)**. It reversibly inhibits the intracellular kinase domains of both **EGFR (ErbB1)** and **HER2/neu (ErbB2)**. By blocking these receptors, it prevents the activation of downstream signaling pathways (like MAPK and PI3K) that promote cell proliferation and survival. It is primarily used in the treatment of HER2-positive advanced or metastatic breast cancer. **Analysis of Incorrect Options:** * **A. Imatinib:** This is the prototype TKI but it targets **BCR-ABL** (Philadelphia chromosome), **c-KIT**, and **PDGFR**. It is the first-line treatment for Chronic Myeloid Leukemia (CML) and Gastrointestinal Stromal Tumors (GIST). * **B. Gefitinib:** This is a selective **EGFR (ErbB1)** inhibitor. It does not have significant activity against HER2. It is primarily used in Non-Small Cell Lung Cancer (NSCLC) with EGFR mutations. * **C. Erlotinib:** Similar to Gefitinib, Erlotinib is a selective **EGFR** inhibitor used in NSCLC and pancreatic cancer. It lacks dual inhibition of HER2. **High-Yield Clinical Pearls for NEET-PG:** * **Trastuzumab vs. Lapatinib:** While both target HER2, Trastuzumab is a monoclonal antibody (extracellular), whereas Lapatinib is a small molecule inhibitor (intracellular). * **Afatinib:** Another drug to remember; it is an *irreversible* ErbB family blocker (inhibits EGFR, HER2, and HER4). * **Side Effects:** A common side effect of EGFR inhibitors (Gefitinib/Erlotinib) is an **acneiform skin rash**, the severity of which often correlates with a positive therapeutic response. Lapatinib is also associated with **diarrhea** and potential **hepatotoxicity**.

Q: Crizotinib is an inhibitor of which receptor?

Tyrosine kinase. **Explanation:** **Crizotinib** is a first-generation, orally active small-molecule inhibitor that primarily targets the **Tyrosine Kinase** domain. Specifically, it inhibits the **ALK (Anaplastic Lymphoma Kinase)** and **ROS1** tyrosine kinases. In certain cancers, chromosomal rearrangements (like the EML4-ALK fusion gene) lead to constitutive activation of tyrosine kinase signaling, driving uncontrolled cell proliferation. Crizotinib binds to the ATP-binding site of these receptors, blocking the downstream oncogenic signaling pathways. **Analysis of Options:** * **Option A (Correct):** Crizotinib is a multi-targeted receptor tyrosine kinase inhibitor (TKI). It is the standard treatment for patients with ALK-positive or ROS1-positive non-small cell lung cancer (NSCLC). * **Option B (Incorrect):** VEGF receptor inhibitors include drugs like **Bevacizumab** (monoclonal antibody) or **Sunitinib/Sorafenib** (TKIs with anti-angiogenic properties). While some TKIs overlap, Crizotinib’s primary clinical utility is not via VEGF inhibition. * **Option C (Incorrect):** TNF-alpha inhibitors are biological DMARDs used in autoimmune conditions (e.g., Rheumatoid Arthritis), such as **Infliximab, Adalimumab,** and **Etanercept**. * **Option D (Incorrect):** PDGF receptor inhibitors include **Imatinib** (which also targets BCR-ABL) and **Olaratumab**. **High-Yield Clinical Pearls for NEET-PG:** 1. **Indication:** First-line for **ALK-positive metastatic NSCLC**. 2. **Resistance:** Patients often develop resistance via the **L1196M "gatekeeper" mutation**; in such cases, second-generation inhibitors like **Ceritinib** or **Alectinib** are used. 3. **Side Effects:** Visual disturbances (flashes of light), hepatotoxicity, and QT interval prolongation. 4. **Diagnostic Marker:** ALK rearrangements are typically detected via **FISH** (Fluorescence In Situ Hybridization) or IHC.

Q: Sorafenib, a tyrosine kinase inhibitor, is used to treat which of the following conditions?

Hepatocellular carcinoma. **Explanation:** **Sorafenib** is a multi-kinase inhibitor that targets several pathways involved in tumor growth and angiogenesis. It primarily inhibits **Raf serine/threonine kinases** (C-Raf, B-Raf) and **Receptor Tyrosine Kinases** (VEGFR-2, VEGFR-3, PDGFR-β). 1. **Why Hepatocellular Carcinoma (HCC) is correct:** Sorafenib was the first systemic therapy proven to extend survival in patients with advanced, unresectable HCC. By inhibiting the Raf/MEK/ERK pathway and blocking VEGF receptors, it effectively reduces tumor proliferation and angiogenesis in the highly vascular environment of the liver. It is also FDA-approved for advanced **Renal Cell Carcinoma (RCC)** and differentiated thyroid cancer. 2. **Why other options are incorrect:** * **Myeloproliferative disorders:** These are typically treated with **Imatinib** (CML - BCR-ABL inhibitor) or **Ruxolitinib** (Polycythemia Vera/Myelofibrosis - JAK2 inhibitor). * **Follicular lymphoma:** This is a B-cell malignancy usually managed with **Rituximab** (anti-CD20 monoclonal antibody) or alkylating agents. * **Medullary carcinoma thyroid:** While Sorafenib is used for *differentiated* thyroid cancer, the drugs of choice for Medullary thyroid cancer are **Vandetanib** or **Cabozantinib** (targeting the RET proto-oncogene). **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Dual action (Antiproliferative via Raf + Anti-angiogenic via VEGFR/PDGFR). * **Key Side Effect:** **Hand-Foot Skin Reaction (HFSR)**—characterized by redness, pain, and hyperkeratosis on palms and soles (distinct from the Hand-Foot Syndrome caused by 5-FU). * **Other Multi-kinase Inhibitors:** **Sunitinib** (used in RCC and GIST) and **Erlotinib/Gefitinib** (EGFR inhibitors used in NSCLC).

Q: Which of the following is a cytoprotective agent against radiation-induced stomatitis?

Amifostine. **Explanation:** **Amifostine (Option A)** is the correct answer. It is a **cytoprotective adjuvant** (a prodrug) that is converted by alkaline phosphatase into an active free thiol metabolite. This metabolite acts as a potent scavenger of free radicals generated by ionizing radiation and certain chemotherapeutic agents (like Cisplatin). Because alkaline phosphatase activity is higher in normal tissues and the pH is more alkaline compared to the acidic tumor microenvironment, Amifostine selectively protects healthy cells. It is FDA-approved to reduce the incidence of **radiation-induced xerostomia (dry mouth)** and **stomatitis** in patients undergoing radiotherapy for head and neck cancer. **Analysis of Incorrect Options:** * **Metronidazole (Option B):** An antibiotic and antiprotozoal agent. While it can act as a radiosensitizer for hypoxic cells, it is not used as a cytoprotective agent against stomatitis. * **Misonidazole (Option C):** A known **radiosensitizer**. It mimics oxygen to increase the sensitivity of hypoxic tumor cells to radiation, making them easier to kill; it does not protect normal tissues. * **Acarbose (Option D):** An alpha-glucosidase inhibitor used in the management of Type 2 Diabetes Mellitus to reduce postprandial hyperglycemia. **High-Yield Clinical Pearls for NEET-PG:** * **Amifostine** also protects against **Cisplatin-induced nephrotoxicity**. * **Mesna** is the cytoprotective agent used to prevent **hemorrhagic cystitis** caused by Cyclophosphamide or Ifosfamide. * **Dexrazoxane** is used to prevent **anthracycline-induced cardiotoxicity** (e.g., Doxorubicin). * **Leucovorin (Folinic acid)** is used as a "rescue" for **Methotrexate** toxicity.

Q: The MDR gene acts by which mechanism?

Causing efflux of drugs. **Explanation:** The **MDR-1 gene** (Multi-Drug Resistance gene 1) encodes for a cell surface glycoprotein known as **P-glycoprotein (P-gp)** [1]. This protein belongs to the ATP-binding cassette (ABC) transporter family [2]. **1. Why Option C is Correct:** The primary mechanism of the MDR-1 gene is the synthesis of P-glycoprotein, which acts as an **ATP-dependent efflux pump** [3]. It actively pumps various hydrophobic anticancer drugs (such as Vinca alkaloids, Anthracyclines, and Taxanes) out of the tumor cell [1]. This reduces the intracellular concentration of the drug to sub-therapeutic levels, leading to resistance. **2. Why Other Options are Incorrect:** * **Option A:** Blocking drug activation is a mechanism seen with drugs like **5-Fluorouracil** or **Cytarabine**, where the cell fails to convert the prodrug into its active metabolite. * **Option B:** Blocking DNA synthesis is the **mechanism of action** of antimetabolites (e.g., Methotrexate), not a mechanism of the MDR gene [4]. * **Option C:** Inhibiting DNA repair is a strategy used by certain drugs (like PARP inhibitors) to kill cancer cells; it is not the function of the MDR gene. **High-Yield Clinical Pearls for NEET-PG:** * **Drugs affected by MDR:** "VATP" — **V**inca alkaloids, **A**nthracyclines (Doxorubicin), **T**axanes (Paclitaxel), and **P**odophyllotoxins (Etoposide) [1]. * **Drugs NOT affected by MDR:** Alkylating agents (Cyclophosphamide) and Antimetabolites. * **P-gp Inhibitors:** Drugs like **Verapamil**, Quinidine, and Cyclosporine can inhibit P-glycoprotein and are sometimes studied to reverse drug resistance. * **Normal Location:** P-gp is also found in the Blood-Brain Barrier (BBB), liver, and kidneys, where it protects normal tissues from toxins [3].

Q: A 56-year-old female with lymph-node-positive breast cancer was treated with systemic chemotherapy. Four weeks later, she developed frequent urination, suprapubic pain, dysuria, and hematuria. Which of the following could have prevented this patient's condition?

Mesna. **Explanation:** The patient is presenting with **Hemorrhagic Cystitis**, a classic adverse effect associated with high-dose **Cyclophosphamide** or **Ifosfamide** therapy (alkylating agents commonly used in breast cancer regimens). These drugs are metabolized into **Acrolein**, a toxic metabolite that accumulates in the bladder, causing direct mucosal damage, inflammation, and bleeding. **Why Mesna is the correct answer:** **Mesna (2-Mercaptoethane sulfonate)** is a sulfhydryl compound that prevents hemorrhagic cystitis through two mechanisms: 1. It binds to and neutralizes acrolein in the urinary tract to form a non-toxic compound. 2. It slows the degradation of 4-hydroxy metabolites of cyclophosphamide. *Note: Vigorous hydration is also essential alongside Mesna.* **Analysis of Incorrect Options:** * **A. Folinic acid (Leucovorin):** Used as a "rescue" therapy to prevent bone marrow suppression after high-dose **Methotrexate** or to potentiate the action of 5-Fluorouracil. * **C. Dexrazoxane:** An iron-chelating agent used to prevent **Anthracycline-induced cardiotoxicity** (e.g., Doxorubicin). * **D. Amifostine:** A cytoprotective free-radical scavenger used to reduce **Cisplatin-induced nephrotoxicity** and xerostomia. **High-Yield Clinical Pearls for NEET-PG:** * **Acrolein** = The culprit for Hemorrhagic Cystitis. * **Mesna** = The specific antidote/preventative agent. * **Ifosfamide** is more urotoxic than Cyclophosphamide; therefore, Mesna is mandatory with Ifosfamide. * **Other uses of Cyclophosphamide:** Apart from cancer, it is used in Wegener’s Granulomatosis (GPA) and Nephrotic syndrome. Long-term risk includes Transitional Cell Carcinoma of the bladder.

Q: Imatinib mesylate is most useful in the treatment of which condition?

Chronic myeloid leukaemia. **Explanation:** **Imatinib mesylate** is the prototype of a class of drugs known as **Tyrosine Kinase Inhibitors (TKIs)**. It is considered the first-line treatment and the "gold standard" for **Chronic Myeloid Leukaemia (CML)**. **Why Option B is Correct:** The hallmark of CML is the **Philadelphia chromosome [t(9;22)]**, which creates the **BCR-ABL fusion gene**. This gene encodes a constitutively active tyrosine kinase protein that drives uncontrolled cellular proliferation. Imatinib works by competitively binding to the ATP-binding site of the BCR-ABL enzyme, inhibiting its activity and inducing apoptosis in leukemic cells. **Why Other Options are Incorrect:** * **A. Chronic Lymphoid Leukaemia (CLL):** The primary treatments involve agents like Fludarabine, Rituximab, or Ibrutinib (a BTK inhibitor), as CLL does not typically involve the BCR-ABL mutation. * **C. Acute Myeloid Leukaemia (AML):** Standard induction therapy is the "7+3" regimen (Cytarabine + Daunorubicin). Imatinib is only used in rare cases of Philadelphia chromosome-positive (Ph+) AML. * **D. Acute Lymphoid Leukaemia (ALL):** While Imatinib is used in **Ph+ ALL** (a specific subtype), it is not the primary treatment for the general category of ALL, which relies on multi-agent chemotherapy (Vincristine, Steroids, L-Asparaginase). **High-Yield Clinical Pearls for NEET-PG:** * **Other Indications:** Imatinib is also the drug of choice for **Gastrointestinal Stromal Tumors (GIST)** by inhibiting the **c-KIT** tyrosine kinase. * **Mechanism:** It is a selective inhibitor of BCR-ABL, c-KIT, and PDGFR. * **Side Effects:** The most characteristic side effect is **periorbital edema** (fluid retention). * **Resistance:** Resistance to Imatinib often occurs due to the **T315I mutation**, which requires newer TKIs like **Ponatinib**.

Q: What is the most common side effect of mycophenolate mofetil?

Diarrhea. **Explanation:** **Mycophenolate Mofetil (MMM)** is a potent immunosuppressant that acts by inhibiting **Inosine Monophosphate Dehydrogenase (IMPDH)**, the rate-limiting enzyme in the *de novo* synthesis of guanosine nucleotides. Since T and B lymphocytes lack the salvage pathway for purine synthesis, they are selectively inhibited. **1. Why Diarrhea is the Correct Answer:** Gastrointestinal (GI) disturbances are the most frequent adverse effects of MMF. Among these, **diarrhea** is the most common (occurring in up to 30-50% of patients), followed by nausea, vomiting, and abdominal pain. This occurs because MMF exerts a direct toxic effect on the rapidly dividing intestinal epithelial cells, which, like lymphocytes, are partially dependent on the *de novo* purine pathway. **2. Why Other Options are Incorrect:** * **Marrow suppression (A):** While MMF can cause leukopenia and anemia, it is generally considered less myelosuppressive than Azathioprine. GI toxicity remains more prevalent. * **Nephrotoxicity (B):** MMF is notably **non-nephrotoxic**. This is a major clinical advantage over Calcineurin Inhibitors (CNIs) like Cyclosporine and Tacrolimus. * **Glucose intolerance (C):** This is a classic side effect of Corticosteroids and Tacrolimus, not MMF. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** Reversible inhibition of IMPDH. * **Clinical Use:** Prophylaxis of transplant rejection (often replacing Azathioprine) and treatment of Lupus Nephritis. * **Teratogenicity:** MMF is highly teratogenic (Category D); it is associated with **congenital malformations** (ear and facial defects). * **Drug Interaction:** Antacids containing magnesium or aluminum hydroxide decrease MMF absorption.

Q: Which of the following are alkylating agents?

Cyclophosphamide. **Explanation:** Alkylating agents are a class of cell cycle-nonspecific antineoplastic drugs that act by forming covalent bonds with DNA, specifically at the **N7 position of guanine**. This results in DNA cross-linking, strand breakage, and inhibition of DNA replication, ultimately leading to cell death (apoptosis). **Why Cyclophosphamide is correct:** **Cyclophosphamide** is a nitrogen mustard and a classic example of an alkylating agent. It is a prodrug activated in the liver by cytochrome P450 enzymes into its active forms, phosphoramide mustard and acrolein. It is widely used in treating lymphomas, leukemias, and solid tumors. **Analysis of Incorrect Options:** * **A. Vincristine:** This is a **Vinca alkaloid** (Antimitotic). It works by binding to tubulin and inhibiting microtubule polymerization, causing cell cycle arrest in the M-phase. * **B. Actinomycin-D (Dactinomycin):** This is an **Antitumor Antibiotic**. It acts by intercalating between DNA base pairs and inhibiting RNA synthesis by blocking RNA polymerase. * **C. Chlorambucil:** While Chlorambucil **is** also an alkylating agent (nitrogen mustard), in the context of single-choice NEET-PG questions, Cyclophosphamide is often the "most representative" or intended answer if only one can be selected. *Note: If this were a multiple-response question, both C and D would be correct.* **High-Yield Clinical Pearls for NEET-PG:** * **Acrolein Toxicity:** The metabolite acrolein causes **Hemorrhagic Cystitis**. This is prevented by aggressive hydration and the administration of **MESNA** (a sulfhydryl compound that neutralizes acrolein). * **Other Alkylating Agents:** Busulfan (causes pulmonary fibrosis), Nitrosoureas (Carmustine/Lomustine - cross the BBB), and Dacarbazine. * **Resistance:** Often occurs due to increased production of glutathione or enhanced DNA repair mechanisms (e.g., MGMT enzyme).

Question 1

A 55-year-old male patient complains of an abnormal growth on his right cheek. The patient has a habit of tobacco chewing for 30 years. Radiologic findings reveal an 8x8 cm fungating mass invading the maxilla and mandible on the right side. The patient was advised palliative chemotherapy with cisplatin. Which of the following changes in DNA is NOT caused by this drug?

Accepted Answer

The changed structure cannot bind proteins

Answer

A-tracts are replaced by other bases

Answer

Collapse of the helix into the minor groove of A-tract

Answer

Production of bent structures in DNA

Question 2

Which of the following drugs acts by inhibiting the tyrosine kinase activated by the EGF receptor as well as HER2?

Accepted Answer

Lapatinib

Answer

Imatinib

Answer

Gefitinib

Answer

Erlotinib

Question 3

Crizotinib is an inhibitor of which receptor?

Accepted Answer

Tyrosine kinase

Answer

VEGF receptor

Answer

TNF alpha receptor

Answer

PDGF receptor

Question 4

Sorafenib, a tyrosine kinase inhibitor, is used to treat which of the following conditions?

Accepted Answer

Hepatocellular carcinoma

Answer

Myeloproliferative disorder

Answer

Follicular lymphoma

Answer

Medullary carcinoma thyroid

Question 5

Which of the following is a cytoprotective agent against radiation-induced stomatitis?

Accepted Answer

Amifostine

Answer

Metronidazole

Answer

Misonidazole

Answer

Acarbose

Question 6

The MDR gene acts by which mechanism?

Accepted Answer

Causing efflux of drugs

Answer

Blocking drug activation

Answer

Blocking intracellular DNA synthesis

Answer

Inhibiting DNA repair

Question 7

A 56-year-old female with lymph-node-positive breast cancer was treated with systemic chemotherapy. Four weeks later, she developed frequent urination, suprapubic pain, dysuria, and hematuria. Which of the following could have prevented this patient's condition?

Accepted Answer

Mesna

Answer

Folinic acid

Answer

Dexrazoxane

Answer

Amifostine

Question 8

Imatinib mesylate is most useful in the treatment of which condition?

Accepted Answer

Chronic myeloid leukaemia

Answer

Chronic lymphoid leukaemia

Answer

Acute myeloid leukaemia

Answer

Acute lymphoid leukaemia

Question 9

What is the most common side effect of mycophenolate mofetil?

Accepted Answer

Diarrhea

Answer

Marrow suppression

Answer

Nephrotoxicity

Answer

Glucose intolerance

Question 10

Which of the following are alkylating agents?

Accepted Answer

Cyclophosphamide

Answer

Vincristine

Answer

Actinomycin-D

Answer

Chlorambucil

Anticancer Drugs — MCQs

Anticancer Drugs — MCQs

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