Anticancer Drugs

Anticancer Drugs Indian Medical PG Question 1: Which of the following drugs act by inhibiting DNA replication?

• A. Mitomycin C
• B. 6-Mercaptopurine (Correct Answer)
• C. Actinomycin D
• D. Asparaginase

Anticancer Drugs Explanation: ***6-Mercaptopurine*** - This drug is a **purine analog** that acts as an **antimetabolite**, directly interfering with the **synthesis of purine nucleotides** required for DNA replication. - By inhibiting enzymes like **PRPP amidotransferase** and getting incorporated into DNA as a fraudulent nucleotide, it blocks the **de novo synthesis** pathway, preventing normal DNA replication. - This represents **direct inhibition of DNA synthesis** at the nucleotide building block level. *Mitomycin C* - This agent is an **alkylating agent** that **cross-links DNA** strands, causing DNA damage that prevents strand separation. - While it does prevent DNA replication, its mechanism is through **DNA damage and structural disruption** rather than inhibition of the DNA synthesis machinery itself. - It acts by damaging already-formed DNA rather than preventing new DNA synthesis. *Actinomycin D* - Actinomycin D is an **intercalating agent** that inserts itself between DNA base pairs, primarily **inhibiting RNA synthesis** by blocking RNA polymerase movement. - While it binds to DNA, its primary therapeutic action is on **transcription (RNA synthesis)**, not direct inhibition of DNA replication. *Asparaginase* - Asparaginase is an enzyme that **depletes asparagine** from the blood, which is an essential amino acid for certain cancer cells (e.g., leukemic cells). - Its mechanism is to starve cancer cells of asparagine, leading to **inhibition of protein synthesis**, not DNA replication.

Anticancer Drugs Indian Medical PG Question 2: All of the following are major subtypes of breast cancer based on Gene array analysis EXCEPT:

• A. Luminal A and Luminal B
• B. Triple negative
• C. Her-2 receptor positive
• D. Estrogen receptor positive (Correct Answer)

Anticancer Drugs Explanation: ***Oestrogen receptor positive*** - While **estrogen receptor (ER) positivity** is a critical prognostic and predictive marker in breast cancer, it is a single marker, not a distinct intrinsic subtype encompassing broader genomic categorization [1]. - The intrinsic subtypes are based on gene expression profiles that cluster tumors into biologically distinct groups, such as Luminal A, Luminal B, HER2-enriched, and Basal-like (including Triple Negative) [3]. *Luminal A and Luminal B* - These are major intrinsic subtypes characterized by the expression of **hormone receptors** (ER and/or PR) and differing in their proliferation rates [2]. - **Luminal A** generally has high ER, low proliferation, and a good prognosis, while **Luminal B** often has higher proliferation (e.g., higher Ki-67) and a slightly worse prognosis [2]. *Triple negative* - This is a major intrinsic subtype (**Basal-like**) defined by the absence of **estrogen receptors (ER)**, **progesterone receptors (PR)**, and **HER2 overexpression** [1], [4]. - It often correlates with a more aggressive clinical course and specific treatment approaches [4]. *Her-2 receptor positive* - This is a major intrinsic subtype characterized by the **overexpression or amplification of the HER2 gene** [3]. - These cancers are often aggressive but respond well to targeted therapies like trastuzumab [3], [4]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, pp. 1064-1066. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 10th ed. The Breast, pp. 1059-1060. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Breast, p. 1060. [4] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 258-259.

Anticancer Drugs Indian Medical PG Question 3: Which of the following is NOT a criterion for defining extensively drug-resistant tuberculosis (XDR-TB)?

• A. Isoniazid + Rifampicin + Fluoroquinolone
• B. Isoniazid + Rifampicin + Ethambutol + Fluoroquinolone
• C. Fluoroquinolone (Correct Answer)
• D. Isoniazid + Rifampicin + Kanamycin

Anticancer Drugs Explanation: ***Fluoroquinolone*** - Resistance to **fluoroquinolone alone** is NOT a criterion for XDR-TB because XDR-TB requires a **baseline of MDR-TB** (resistance to both rifampicin and isoniazid) plus additional resistances. - XDR-TB definition (WHO 2021): **MDR-TB** + resistance to **any fluoroquinolone** + resistance to **at least one Group A drug** (bedaquiline or linezolid). - Fluoroquinolone resistance in isolation does not meet any of these combined criteria. *Isoniazid + Rifampicin + Fluoroquinolone* - This represents **MDR-TB** (rifampicin + isoniazid resistance) plus **fluoroquinolone resistance**. - This is a partial criterion approaching XDR-TB but still requires additional resistance to at least one Group A drug (bedaquiline or linezolid) for complete XDR-TB classification. - However, this combination includes the essential MDR-TB base and fluoroquinolone component. *Isoniazid + Rifampicin + Ethambutol + Fluoroquinolone* - This includes **MDR-TB** (rifampicin + isoniazid), **fluoroquinolone resistance**, and ethambutol (first-line drug). - While ethambutol resistance alone doesn't define XDR-TB, this combination includes the critical MDR-TB and fluoroquinolone components required for XDR-TB classification. - Similar to above, would need Group A drug resistance for complete XDR-TB. *Isoniazid + Rifampicin + Kanamycin* - This represents **MDR-TB** plus resistance to **kanamycin** (a second-line injectable). - Under previous WHO definitions (pre-2021), injectable resistance was part of XDR-TB criteria. - This combination includes the MDR-TB base essential for any XDR-TB classification, though it lacks fluoroquinolone resistance.

Anticancer Drugs Indian Medical PG Question 4: A 55-year-old woman with non-small cell lung cancer is found to have an ALK gene rearrangement. How should this finding influence her treatment?

• A. Refer for surgical resection, if appropriate
• B. Switch to crizotinib, a targeted ALK inhibitor (Correct Answer)
• C. Consider radiation therapy, if indicated
• D. Continue standard chemotherapy, if appropriate for the patient's condition

Anticancer Drugs Explanation: ***Switch to crizotinib, a targeted ALK inhibitor*** - The presence of an **ALK gene rearrangement** in **non-small cell lung cancer (NSCLC)** is a strong indicator for **targeted therapy** with an **ALK inhibitor** like crizotinib. - These drugs specifically block the aberrant activity of the ALK fusion protein, leading to **superior response rates** and **progression-free survival** compared to standard chemotherapy in ALK-positive patients. *Refer for surgical resection, if appropriate* - **Surgical resection** is primarily considered for **early-stage NSCLC** without evidence of metastatic disease [1]. - While surgery can be curative, the presence of specific gene rearrangements like ALK typically prompts consideration of **neoadjuvant or adjuvant targeted therapy** or systemic therapy for advanced disease. *Consider radiation therapy, if indicated* - **Radiation therapy** for NSCLC is usually employed for **local control**, either in curative intent for early stages or for **palliative management** of symptoms in advanced disease [2]. - It does not directly address the underlying **genetic driver** (ALK rearrangement) and would not be the primary systemic treatment. *Continue standard chemotherapy, if appropriate for the patient's condition* - While **standard chemotherapy** is a treatment option for NSCLC, the identification of a **driver mutation** like an ALK rearrangement makes **targeted therapy** a significantly more effective and preferred first-line approach. - Continuing chemotherapy without considering targeted therapy would be **suboptimal** for a patient with an ALK rearrangement due to the availability of more effective treatments.

Anticancer Drugs Indian Medical PG Question 5: Which of the following is a monoclonal antibody used in cancer treatment?

• A. Cisplatin
• B. Rituximab (Correct Answer)
• C. 5-fluorouracil
• D. Methotrexate

Anticancer Drugs Explanation: ***Rituximab*** - **Rituximab** is a **chimeric monoclonal antibody** that targets the **CD20 protein** found on the surface of normal and malignant **B lymphocytes**. - It is widely used in the treatment of various **lymphomas** and **leukemias**, as well as autoimmune diseases, by inducing the death of CD20-positive B cells. *Cisplatin* - **Cisplatin** is a **platinum-based chemotherapy drug** that works by forming **DNA adducts**, leading to DNA damage and apoptosis of cancer cells. - It is used in various solid tumors but is not a monoclonal antibody; it's a **cytotoxic agent**. *5-fluorouracil* - **5-fluorouracil (5-FU)** is an **antimetabolite chemotherapy drug** that interferes with DNA and RNA synthesis, thereby inhibiting cell division. - It is a **pyrimidine analog** and not a monoclonal antibody. *Methotrexate* - **Methotrexate** is a **folate analog antimetabolite** that inhibits **dihydrofolate reductase**, interfering with DNA synthesis and cell proliferation. - It's a conventional chemotherapy agent and immunosuppressant, not a monoclonal antibody.

Anticancer Drugs Indian Medical PG Question 6: Which is the most cardiotoxic anti-cancer drug among the following?

• A. Cyclophosphamide
• B. Tamoxifen
• C. Imatinib
• D. Anthracyclines (Correct Answer)

Anticancer Drugs Explanation: ***Anthracyclines*** - **Anthracyclines** (e.g., doxorubicin, daunorubicin) are notorious for causing **dose-dependent cardiotoxicity**, leading to **irreversible dilated cardiomyopathy** and **heart failure**. - Their cardiotoxic effect is primarily due to the generation of **reactive oxygen species** and interference with cardiac topoisomerase IIβ. *Cyclophosphamide* - Cyclophosphamide can cause cardiotoxicity, particularly at **high doses**, manifesting as **hemorrhagic myocardial necrosis** or **pericarditis**. - However, its cardiotoxicity is generally considered **less frequent and severe** than that of anthracyclines. *Tamoxifen* - Tamoxifen is primarily associated with an **increased risk of thromboembolic events** and **endometrial cancer**. - While some cardiac effects like **QT prolongation** can occur, it is not considered a primary cardiotoxic agent leading to cardiomyopathy. *Imatinib* - Imatinib, a **tyrosine kinase inhibitor**, has been linked to **cardiac dysfunction** including heart failure in some patients. - However, the incidence and severity of cardiotoxicity with imatinib are **lower** compared to anthracyclines, which are broadly cardiotoxic.

Anticancer Drugs Indian Medical PG Question 7: Treatment with Herceptin in breast cancer is indicated for

• A. Tumours with over-expressed HER2/C-erbB-2 protein (Correct Answer)
• B. PR receptor +ve tumours
• C. ER receptor +ve tumours
• D. Ki-67 stain +ve tumours

Anticancer Drugs Explanation: **tumours with over-expressed C-erb B-2 protein** - **Herceptin** (trastuzumab) is a monoclonal antibody that specifically targets the **HER2/neu receptor**, which is encoded by the *ERBB2* gene. - Its efficacy depends on the **overexpression of C-erbB-2 protein** (also known as HER2/neu) on the surface of breast cancer cells, which indicates **HER2-positive breast cancer**. *K : 67 stain +ve tumours* - **Ki-67** is a proliferation marker that indicates the **growth fraction of a tumor**, and a positive stain suggests a rapidly dividing tumor. - While Ki-67 positivity is associated with more aggressive tumors, it does **not directly indicate suitability for Herceptin** treatment. *PR receptor +ve tumours* - Tumors positive for the **progesterone receptor (PR)** are typically treated with **hormonal therapies**, such as tamoxifen or aromatase inhibitors. - **PR positivity** does not indicate responsiveness to Herceptin, which targets the HER2 receptor. *ER receptor +ve tumours* - Tumors positive for the **estrogen receptor (ER)** are also treated with **hormonal therapies** due to their dependence on estrogen for growth. - Similarly to PR-positive tumors, **ER positivity** does not determine eligibility for Herceptin therapy.

Anticancer Drugs Indian Medical PG Question 8: What is the treatment for HER-2 positive trastuzumab resistant breast cancer?

• A. Sorafenib
• B. Lapatinib (Correct Answer)
• C. Vemurafenib
• D. Erlotinib

Anticancer Drugs Explanation: ***Lapatinib*** - Lapatinib is a **dual tyrosine kinase inhibitor** that targets both **HER-2** and **epidermal growth factor receptor (EGFR)**, acting as a **small molecule inhibitor** that binds to the intracellular domain of these receptors. - Unlike trastuzumab (a monoclonal antibody targeting the extracellular domain), Lapatinib's **intracellular mechanism of action** allows it to overcome common mechanisms of trastuzumab resistance, such as receptor truncation or masking of the extracellular epitope. - It is specifically approved for the treatment of **HER-2 positive metastatic breast cancer** in combination with capecitabine after progression on trastuzumab-containing regimens. *Sorafenib* - Sorafenib is a **multi-kinase inhibitor** primarily targeting RAF, VEGFR, and PDGFR, and is used in renal cell carcinoma and hepatocellular carcinoma. - It does not specifically target HER-2 and is **not indicated** for HER-2 positive trastuzumab-resistant breast cancer. *Vemurafenib* - Vemurafenib is a **BRAF inhibitor** used for treating BRAF V600E mutation-positive melanoma. - This drug has no direct indications or demonstrated efficacy for **HER-2 positive breast cancer** and does not address trastuzumab resistance mechanisms. *Erlotinib* - Erlotinib is an **EGFR tyrosine kinase inhibitor** primarily used for non-small cell lung cancer with activating EGFR mutations. - While it targets EGFR, it does **not effectively target HER-2** and lacks the dual inhibition necessary to overcome trastuzumab resistance in HER-2 positive breast cancer.

Anticancer Drugs Indian Medical PG Question 9: Mechanism of action of Abatacept is?

• A. T cell inhibitor (Correct Answer)
• B. TNF-alpha inhibitor
• C. Calcineurin inhibitor
• D. IL-1 inhibitor

Anticancer Drugs Explanation: ***T cell inhibitor*** * **Abatacept** works by blocking the **costimulatory signal (CD28-CD80/86)** required for full T-cell activation, acting as a **selective T-cell costimulation modulator** [1]. * This inhibition prevents T-cell proliferation and cytokine production, thereby reducing inflammation in autoimmune diseases. * *TNF-alpha inhibitor* * **TNF-alpha inhibitors** like etanercept or infliximab bind to and neutralize **tumor necrosis factor-alpha (TNF-alpha)**, a key pro-inflammatory cytokine. * While effective in similar conditions, this is a different mechanism of action than Abatacept's direct T-cell modulation. * *Calcineurin inhibitors* * **Calcineurin inhibitors** such as cyclosporine and tacrolimus block the activity of **calcineurin**, an enzyme essential for T-cell activation and cytokine production. * This inhibition primarily prevents **interleukin-2 (IL-2)** transcription, which is crucial for T-cell proliferation, but differs from Abatacept's blocking of costimulation. * *IL-1 inhibitor* * **IL-1 inhibitors** like anakinra target and block the action of **interleukin-1 (IL-1)**, another potent pro-inflammatory cytokine. * This class of drugs is used for conditions driven by IL-1, but their mechanism is distinct from Abatacept's focus on T-cell costimulation.

Anticancer Drugs Indian Medical PG Question 10: What do A and B represent in the curve shown below?

• A. A= Median effective dose, B= Median lethal dose (Correct Answer)
• B. A= Therapeutic index, B= Median efficacy
• C. A= Median lethal dose, B= Median effective dose
• D. A= Median efficacy, B= Therapeutic index

Anticancer Drugs Explanation: ***A= Median effective dose, B= Median lethal dose*** - **A** corresponds to the **median effective dose (ED50)**, which is the dose that produces a therapeutic effect in 50% of the population - The purple curve represents the dose-response for efficacy; at A, 50% of individuals are responding effectively - **B** corresponds to the **median lethal dose (LD50)**, which is the dose that is lethal to 50% of the population - The red curve represents the dose-response for toxicity/lethality; at B, 50% of individuals are experiencing a lethal outcome *A= Therapeutic index, B= Median efficacy* - The **therapeutic index** is a ratio (LD50/ED50), not a specific dose represented on the x-axis - **Median efficacy** is not a standard pharmacological term to represent a point on a dose-response curve; rather, efficacy refers to the maximal effect a drug can produce *A= Median lethal dose, B= Median effective dose* - This option reverses the correct identification of A and B - **Median effective dose (ED50)** is typically expected at lower doses, while **median lethal dose (LD50)** is at higher doses, indicating toxicity - In the provided graph, the curve for A occurs at a much lower dose range than the curve for B, making it the effective dose, not the lethal dose *A= Median efficacy, B= Therapeutic index* - **Median efficacy** is not a specific dose value represented this way on a dose-response curve - The **therapeutic index** is a ratio, not a dose point on the graph

Anticancer Drugs Flashcard 1 of 10

Question: _____ is indicated as a first-line treatment for the management of unresectable hepatocellular carcinoma

Answer: Sorafenib

Anticancer Drugs Flashcard 2 of 10

Question: -Posides (Topoisomerase II inhibitor antineoplastics) are used to treat solid tumors, particularly _____ cancer and small cell lung cancer

Answer: testicular

Anticancer Drugs Flashcard 3 of 10

Question: Drug of choice for EGFR T790M mutation of Non-Small Cell Lung Cancer is

Answer: Osimertinib

Anticancer Drugs Flashcard 4 of 10

Question: Methotrexate resistance is due to the overproduction of _____

Answer: DHFR.

Anticancer Drugs Flashcard 5 of 10

Question: Monitoring of the methotrexate therapy is done every 2-3 months with CBC, LFTs, and serum _____.

Answer: creatinine

Anticancer Drugs Flashcard 6 of 10

Question: _____ is a dual inhibitor of epidermal growth factor (EGFR) and human epidermal growth factor 2 (HER 2) tyrosine kinase.

Answer: Lapatinib

Anticancer Drugs Flashcard 7 of 10

Question: Radiation recall syndrome is associated with the use of which anti-cancer drugs?_____

Answer: Anthracyclines

Anticancer Drugs Flashcard 8 of 10

Question: The new FDA-approved immune checkpoint inhibitor for carcinoma endometrium is _____.

Answer: pembrolizumab

Anticancer Drugs Flashcard 9 of 10

Question: Antineoplastic agents extracted from the Periwinkle plant is: _____ also called Catharanthus roseus

Answer: Vinca alkaloids

Anticancer Drugs Flashcard 10 of 10

Question: Cetuximab is a monoclonal antibody against the _____ Receptor most commonly used to treat Stage IV colorectal cancer

Answer: EGF