Anticancer Drugs — MCQs

Anticancer Drugs Indian Medical PG Practice Questions and MCQs

Question 311: Which of the following drugs acts by inhibiting the tyrosine kinase activated by the EGF receptor as well as HER2?

A. Imatinib
B. Gefitinib
C. Erlotinib
D. Lapatinib (Correct Answer)

Explanation: ### 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**.

Question 312: Crizotinib is an inhibitor of which receptor?

A. Tyrosine kinase (Correct Answer)
B. VEGF receptor
C. TNF alpha receptor
D. PDGF receptor

Explanation: **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.

Question 313: Sorafenib, a tyrosine kinase inhibitor, is used to treat which of the following conditions?

A. Myeloproliferative disorder
B. Follicular lymphoma
C. Medullary carcinoma thyroid
D. Hepatocellular carcinoma (Correct Answer)

Explanation: **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).

Question 314: Which of the following is a cytoprotective agent against radiation-induced stomatitis?

A. Amifostine (Correct Answer)
B. Metronidazole
C. Misonidazole
D. Acarbose

Explanation: **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.

Question 315: The MDR gene acts by which mechanism?

A. Blocking drug activation
B. Blocking intracellular DNA synthesis
C. Causing efflux of drugs (Correct Answer)
D. Inhibiting DNA repair

Explanation: **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].

Question 316: 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?

A. Folinic acid
B. Mesna (Correct Answer)
C. Dexrazoxane
D. Amifostine

Explanation: **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.

Question 317: Imatinib mesylate is most useful in the treatment of which condition?

A. Chronic lymphoid leukaemia
B. Chronic myeloid leukaemia (Correct Answer)
C. Acute myeloid leukaemia
D. Acute lymphoid leukaemia

Explanation: **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**.

Question 318: Ifosfamide belongs to which class of anticancer drugs?

A. Alkylating agent (Correct Answer)
B. Antimetabolite
C. Taxanes
D. Antibiotics

Explanation: **Explanation:** **Ifosfamide** is a nitrogen mustard derivative and a structural isomer of cyclophosphamide. It belongs to the **Alkylating Agents** class of anticancer drugs. 1. **Why it is correct:** Alkylating agents work by attaching an alkyl group to DNA, typically at the **N7 position of guanine**. This leads to DNA cross-linking (inter-strand and intra-strand), which inhibits DNA replication and transcription, eventually triggering apoptosis. Like cyclophosphamide, ifosfamide is a **prodrug** that requires activation by hepatic cytochrome P450 enzymes (specifically CYP3A4 and CYP2B6) to form its active metabolite, ifosfamide mustard. 2. **Why other options are incorrect:** * **Antimetabolites (e.g., Methotrexate, 5-FU):** These interfere with DNA synthesis by acting as structural analogues of folic acid, purines, or pyrimidines. * **Taxanes (e.g., Paclitaxel, Docetaxel):** These are microtubule stabilizers that prevent the disassembly of the mitotic spindle. * **Antibiotics (e.g., Doxorubicin, Bleomycin):** These are microbial-derived agents that act via intercalation or free radical production. **High-Yield Clinical Pearls for NEET-PG:** * **Acrolein Toxicity:** The metabolism of ifosfamide releases **acrolein**, which causes **hemorrhagic cystitis**. This risk is higher with ifosfamide than with cyclophosphamide. * **Prevention:** Hemorrhagic cystitis is managed with aggressive hydration and **MESNA** (2-Mercaptoethane sulfonate Na), which neutralizes acrolein in the bladder. * **Encephalopathy:** Ifosfamide can cause unique CNS toxicity (confusion, seizures) due to the metabolite **chloroacetaldehyde**. * **Spectrum:** It is particularly used in germ cell testicular tumors, sarcomas, and lymphomas.

Question 319: Which of the following inhibits mitosis by forming microtubules?

A. Vinca alkaloids
B. Docetaxel (Correct Answer)
C. Etoposide
D. Colchicine

Explanation: **Explanation:** The correct answer is **Docetaxel**. To understand this, it is essential to distinguish between drugs that prevent the assembly of microtubules and those that prevent their disassembly. **1. Why Docetaxel is correct:** Docetaxel belongs to the **Taxane** group (along with Paclitaxel). These drugs act as **"Microtubule Stabilizers."** They bind to the $\beta$-tubulin subunit and promote the polymerization (formation) of microtubules. However, they inhibit the **depolymerization** (breakdown) process. This results in the formation of non-functional, overly stable microtubule bundles, freezing the cell in the M-phase (specifically anaphase) and leading to apoptosis. **2. Why the other options are incorrect:** * **Vinca alkaloids (e.g., Vincristine, Vinblastine):** These are **"Microtubule Destabilizers."** They bind to tubulin and **prevent the formation** (polymerization) of microtubules. Without microtubule assembly, the mitotic spindle cannot form. * **Colchicine:** Similar to Vinca alkaloids, it inhibits tubulin polymerization. While it inhibits mitosis, it is primarily used for gout, not as a standard systemic anticancer chemotherapy. * **Etoposide:** This is a **Topoisomerase II inhibitor**. It acts on the S and G2 phases of the cell cycle by causing DNA strand breaks, not by affecting microtubules. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic for Taxanes:** "Taxanes **T**erribly **T**ighten" the microtubules (prevent breakdown). * **Mnemonic for Vincas:** "Vincas **V**anquish" the microtubules (prevent formation). * **Specific Side Effects:** * **Docetaxel:** Notable for causing **fluid retention** (peripheral edema). * **Paclitaxel:** Peripheral neuropathy and hypersensitivity reactions (pre-medicate with steroids/antihistamines). * **Vincristine:** Dose-limiting neurotoxicity (peripheral neuropathy and paralytic ileus); notably **bone marrow sparing**.

Question 320: Cardiomyopathy is a side effect caused by which of the following drugs?

A. Adriamycin (Correct Answer)
B. Emetine
C. Paclitaxel
D. Vincristine

Explanation: **Explanation:** **Adriamycin (Doxorubicin)** is the correct answer. It belongs to the Anthracycline class of antibiotics. The hallmark toxicity of anthracyclines is **cardiotoxicity**, which manifests in two forms: 1. **Acute:** Transient ECG changes (arrhythmias). 2. **Chronic:** Dose-dependent, irreversible **Dilated Cardiomyopathy** leading to Congestive Heart Failure (CHF). * **Mechanism:** The cardiotoxicity is mediated by the generation of **iron-dependent free radicals** (superoxide anions) that cause lipid peroxidation of the myocardial cell membrane. The heart is particularly vulnerable because it has low levels of the protective enzyme **catalase**. **Analysis of Incorrect Options:** * **B. Emetine:** While historically known to cause ECG changes and precordial pain, it is an amoebicide, not a standard anticancer drug, and is rarely used today due to its toxicity profile. * **C. Paclitaxel:** The primary dose-limiting toxicity is **peripheral neuropathy** and bone marrow suppression. While it can cause transient bradycardia, it does not typically cause cardiomyopathy. * **D. Vincristine:** This Vinca alkaloid is classic for causing **peripheral neuropathy** (paresthesia, loss of deep tendon reflexes) and autonomic dysfunction (constipation/paralytic ileus). It is notably **bone marrow sparing**. **High-Yield Clinical Pearls for NEET-PG:** * **Dexrazoxane:** An iron chelator used to prevent/reduce Adriamycin-induced cardiotoxicity. * **Lifetime Dose Limit:** To minimize cardiomyopathy risk, the cumulative dose of Doxorubicin should be kept below **450–550 mg/m²**. * **Monitoring:** Periodic **ECHO/MUGA scans** are mandatory to monitor the Left Ventricular Ejection Fraction (LVEF).

Practice by Chapter

Principles of Cancer Chemotherapy

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Alkylating Agents

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Antimetabolites

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Antitumor Antibiotics

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Plant Alkaloids

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Topoisomerase Inhibitors

Practice Questions

Hormonal Agents

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Targeted Therapy

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Immunotherapy

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Management of Chemotherapy Side Effects

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