Cancer Pharmacotherapy Quiz

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Questions and Answers

What is the primary mechanism of action of Imatinib?

Inhibits CD20 protein

Inhibits VEGF

Inhibits BCR-ABL tyrosine kinase (correct)

Inhibits PD-1 protein

Which monoclonal antibody is specifically indicated for HER2 positive breast cancer?

Bevacizumab

Cetuximab

Trastuzumab (correct)

Rituximab

What type of cancer is Bevacizumab used to treat?

Hodgkin lymphoma

Non-Hodgkin lymphoma

Colorectal cancer (correct)

Breast cancer

What is a common adverse effect of Imatinib?

Fluid retention Signup and view all the answers

Which of the following agents are classified as biological response modifiers?

Interferons Signup and view all the answers

What is the main goal of treatment in advanced stages of cancer?

Palliation of symptoms and improved quality of life Signup and view all the answers

Which therapy is particularly useful when tumors are not operable?

Palliative therapy Signup and view all the answers

What is a key advantage of combination chemotherapy?

Maximal cell killing while managing toxicity Signup and view all the answers

Which of the following is not a mechanism of drug resistance in chemotherapy?

Enhanced apoptotic signaling Signup and view all the answers

What type of chemotherapy is used before surgery to reduce tumor size?

Neoadjuvant chemotherapy Signup and view all the answers

Which type of chemotherapy is given to prevent recurrence after surgery?

Adjuvant chemotherapy Signup and view all the answers

What is one of the reasons combination chemotherapy is often more effective than monotherapy?

It delays resistance to treatment Signup and view all the answers

Which of the following is not a form of pharmacotherapy in cancer treatment?

Radiation therapy Signup and view all the answers

What is a common side effect of methotrexate (MTX) that requires monitoring?

Bone marrow depression Signup and view all the answers

Which of the following is NOT a therapeutic application of methotrexate?

Thyroid cancer Signup and view all the answers

Why is it important to keep the urine alkaline for patients taking methotrexate?

To reduce the risk of crystalluria Signup and view all the answers

What is the primary mechanism of action of 6-mercaptopurine (6-MP)?

Interference with purine nucleotide synthesis Signup and view all the answers

Which type of cancer is Paclitaxel notably used to treat?

Ovarian cancer Signup and view all the answers

What adverse effect is associated with the use of doxorubicin?

Cardiotoxicity Signup and view all the answers

What is the primary mechanism of action of Vinca alkaloids?

Disrupt microtubule formation Signup and view all the answers

What is a key enzyme involved in the metabolism of 6-mercaptopurine, which impacts its safety?

Thiopurine S-methyltransferase Signup and view all the answers

What is a common adverse effect of both Paclitaxel and Docetaxel?

Neutropenia Signup and view all the answers

What is the mechanism of action of methotrexate?

Inhibits dihydrofolate reductase Signup and view all the answers

Which antibiotic is known to cause pulmonary fibrosis as a major adverse effect?

Bleomycin Signup and view all the answers

What is the effect of administering allopurinol in conjunction with 6-mercaptopurine?

It causes severe toxicity Signup and view all the answers

Which of the following adverse effects is specifically associated with cyclophosphamide?

Hemorrhagic cystitis Signup and view all the answers

Which of the following describes the action of taxanes like Paclitaxel?

Prevent tubulin polymerization Signup and view all the answers

What specific toxicity is linked to Vincristine?

Peripheral neuropathy Signup and view all the answers

What is a common use of cisplatin?

Testicular tumors Signup and view all the answers

What is a characteristic of hormone-dependent tumors?

They depend on specific hormones for growth Signup and view all the answers

Which agent can ameliorate the adverse effects of cyclophosphamide?

Mesna Signup and view all the answers

What effect do microtubule inhibitors have during the cell cycle?

They cause arrest during metaphase Signup and view all the answers

Which class of drugs does methotrexate belong to?

Antimetabolites Signup and view all the answers

Which adverse effect is common to both cyclophosphamide and cisplatin?

Alopecia Signup and view all the answers

Which adverse effect is considered dose-limiting for taxanes?

Leukopenia Signup and view all the answers

What is the specific target of methotrexate's action?

Dihydrofolate reductase Signup and view all the answers

What mechanism allows tumor cells to resist the effects of methotrexate?

Changes in drug sensitivity of dihydrofolate reductase Signup and view all the answers

Which of the following statements is true regarding the mechanism of cisplatin?

It causes DNA cross-linking Signup and view all the answers

Which of the following anticancer drugs is categorized as an alkylating agent?

Cisplatin Signup and view all the answers

What is a common side effect shared by many cytotoxic anticancer drugs?

Hepatotoxicity Signup and view all the answers

How do tumor cells decrease the activation of prodrugs such as mercaptopurine?

By reducing the synthesis of activation enzymes Signup and view all the answers

What is the mechanism by which alkylating agents exert their cytotoxic effects?

DNA cross-linking Signup and view all the answers

Which of the following statements about P-glycoprotein is accurate?

It is involved in the efflux of anticancer drugs. Signup and view all the answers

What can be a consequence of the mutagenic properties of cytotoxic anticancer drugs?

Development of secondary malignancies Signup and view all the answers

Which class of drugs does not belong to the category of anticancer agents?

Glucosamine Signup and view all the answers

Study Notes

Lecture 8: Anticancer Drugs

Anticancer drugs target specific areas of cell function vital to cancer cell proliferation and halting its growth.
This lecture covers alkylating agents, antimetabolites, and mitotic inhibitors.
The lecture is presented by Matin A. Mahmood; M.Sc. Pharmacology & Toxicology Ph.D. Pharmacology.

Hallmarks of Cancer

Rapid uncontrolled cell proliferation
Malignant transformation
Resistance to apoptosis
Inducing angiogenesis
Invasion and metastasis
Loss of function
Avoiding immune destruction

Proliferation, Differentiation, Undifferentiation

Cells have different stages: differentiated, doubling time and undifferentiated.
Malignant transformation leads to a loss of differentiation and uncontrolled proliferation.

Cell Cycle Regulators

Cell cycle regulators are classified as positive or negative controls.
Positive regulators include growth factors and protein kinase receptors.
Negative regulators include P53 and BRCA1, BRCA2.
A diagram showing the cell cycle and checkpoints is included.

Cancer Cell Cycle Kinetics

Some anticancer drugs (CCS) are specific for cycling cells while others (CCNS) act on both cycling and resting cells, although cycling cells are more sensitive.
Different drugs are usually more effective when cells are in specific phases of the cell cycle.

Cancer Cell Cycle Kinetics (Diagram)

Cell cycle (as a clock) depicting the different phases, such as G0, G1, S, G2, M, with percentages of the cell cycle spent in each phase.

Principles of Cancer Chemotherapy

Cancer chemotherapy aims to eliminate cancer cells through cytotoxic events or apoptosis or arrest the growth of the tumor.
The attack is targeted towards DNA and metabolic sites essential for cell replication.

Anticancer Drugs and Their Effects

Ideally, anticancer drugs target unique aspects of malignant cells.
Existing drugs affect all proliferating cells, both normal and abnormal.
This characteristic of varying effects results in a steep dose-response curve for both therapeutic and toxic outcomes.
Newer methods aim to use a patient's own immune system to target cancer cells.

Treatment Strategies

The ultimate goal of chemotherapy is long-term, disease-free survival.
A cure requires eliminating every neoplastic cell.
If a cure isn't possible, controlling the disease's progression, extending survival and maintaining quality of life.
Cancer is treated as a chronic disease, allowing for quality of life.

Overview of Treatment Strategies

The initial neoplastic burden may be reduced with surgery, radiation, chemotherapy, immunotherapy, etc or a combination of these methods.
In advanced stages, palliation (managing symptoms) is the goal, alongside the avoidance of life-threatening toxic effects.
This helps improve the quality of life, though survival may not be extended.

Cancer Treatment Options

Cancer treatment options include surgery, radiation, chemotherapy, hormonal therapy, immunotherapy, bone marrow transplantation, and palliative therapy.

Indications for Treatment

Chemotherapy is used when neoplasms are not treatable through surgery, or for supplemental treatment of micrometastases following initial treatments.
It can be administered prior to surgery to shrink the tumor.
Lower doses are sometimes used to maintain remission

Treatment Protocols

Combination chemotherapy is often more successful than single-drug treatment for cancer.
Combining drugs with various toxicities and mechanisms of action, at full doses is usually best.
Similar toxicities from specific drugs can be managed by adjusting dosages.

Resistance to Anticancer Drugs

Drug resistance, a major problem in cancer chemotherapy, has several mechanisms.
Increased DNA repair: resistance to alkylating agents and cisplatin.
Formation of trapping agents: increased glutathione in some cancers reducing the efficacy of certain types of anticancer drugs
Changes in target enzymes
Decreased activation of prodrugs
Reduced drug accumulation: The MDR1 gene, which leads to increased expression of protein-glycoprotein, can lower drug efficacy
Different mechanisms of resistance to anticancer drugs, like increased DNA repair or the formation of trapping agents.

Adverse Effects of Anticancer Drugs

Common adverse effects (AEs) of anticancer drugs (ACDs) include bone marrow toxicity (myelosuppression), impaired wound healing, hair loss, damage to gastrointestinal (GI) epithelium, sterility, and liver damage (hepatotoxicity).
Some drugs cause teratogenic and carcinogenic effects

Classes of Anticancer Drugs

Anticancer drugs are divided into several classes, including alkylating agents, antimetabolites, cytotoxic antibiotics, microtubule inhibitors, hormone antagonists, monoclonal antibodies, tyrosine kinase inhibitors, and miscellaneous agents.

Alkylating Agents

Alkylating agents, such as nitrogen mustards (chlorambucil, cyclophosphamide), nitrosoureas (carmustine), and platinum compounds (cisplatin), work by DNA cross-linking.
Alkylation of DNA is probably the crucial cytotoxic reaction that kills the tumor cells. Alkylating agents work even against resting cells and are thus used in combination with other anticancer drugs.
The use of alkylating agents can result in toxic effects such as secondary malignancies.
Different types of alkylating agents are introduced for different uses.
Cyclophosphamide example: is the most commonly used alkylating agent, but is an activated prodrug. Its side effects include bone marrow suppression, hepatotoxicity, and alopecia; hemorrhagic cystitis may result from the byproducts ifosfamide and acetaminophen.

Cisplatin

Cisplatin: Platinum compound, DNA cross-linking, testicular and ovarian cancers.
General adverse events: Bone marrow depression (mild), hepatotoxicity, alopecia and nausea/vomiting.
Specific adverse events: nephrotoxicity, sensory hearing loss, and peripheral neuropathy.

Antimetabolites

Antimetabolites are structurally similar to normal metabolites but disrupt normal cell processes.
Examples include methotrexate (folic acid antagonist) and 6-mercaptopurine, 5-fluorouracil (purine and pyrimidine analogues). These agents disrupt DNA and RNA synthesis.

Methotrexate (MTX)

Mechanism of action: MTX inhibits dihydrofolate reductase, an enzyme essential for the production of tetrahydrofolic acid.
This prevents the synthesis of purines, pyrimidines, and thymidylate.
It works by inhibiting folate metabolism and therefore DNA synthesis.
Therapeutic uses: MTX is used in combination with other drugs or as a low-dose single agent for specific types of cancer and certain inflammatory conditions.
Pharmacokinetics: MTX is variably absorbed from the gastrointestinal tract, and its metabolite is less water soluble than MTX, which may lead to crystalluria. Urine alkalinization and patient hydration are important to avoid renal toxicity. Adverse effects: Bone marrow depression, hepatotoxicity, teratogenicity, megaloblastic anemia, and mucosal ulceration. Folinic acid supplementation is used to prevent megaloblastic anemia.

6-Mercaptopurine (6-MP)

Mechanism of action: Interferes with purine nucleotide synthesis, inhibiting DNA and RNA synthesis.
Adverse effects: Bone marrow depression, hepatotoxicity, and teratogenicity.
Specific adverse effects: the enzyme thiopurine S-methyltransferase (TPMT) converts 6-MP into a nontoxic compound. Some patients have genetic TPMT deficiency, consequent severe adverse events (myelosuppression). Concomitant use of allopurinol (xanatine oxidase inhibitor)with this type of drug can lead to severe toxicity due to its interference with xanthine metabolism

Antibiotics (Doxorubicin)

The cytotoxic action of antibiotics, such as doxorubicin, is often due to their interactions with DNA.
Doxorubicin inhibits DNA and RNA synthesis.
The main adverse effect of doxorubicin is irreversible, dose-dependent cardiotoxicity which is caused from free radical formation causing lipid peroxidation
Other anticancer antibiotics like bleomycin and mitomycin C, also have different mechanisms and adverse effects like pulmonary fibrosis and nephrotoxicity.

Microtubule Inhibitors (Vinca Alkaloids)

Mitotic spindle components: essential for accurate cell division
Vinca alkaloids (vincristine, vinblastine): block the proper functioning of the mitotic spindle.
Adverse effects: general effects such as hepatotoxicity and alopecia, and less commonly neurotoxicity.
Paclitaxel and docetaxel: Plant-derived substances that also target microtubules. Paclitaxel was the first taxane used in chemotherapy for treating cancer. Paclitaxel and docetaxel are valuable drugs in treating various types of cancer.

Hormones and Hormone Antagonists

Some cancers are hormone dependent (breast, prostate).
Hormone antagonists (tamoxifen, aromatase inhibitors, antiandrogens) are used to interrupt the hormone's effect on cancer cell growth.
Tamoxifen: Selective estrogen receptor modulator (SERM), used in estrogen receptor-positive breast cancer treatment. Adverse effects include endometrial cancer risk and thrombotic complications.
Aromatase inhibitors (anastrozole, letrozole): Inhibit estrogen production. Useful in postmenopausal women with ER-positive breast cancer.
Antiandrogens (flutamide, cyproterone acetate): Block testosterone action. Used in prostate cancer. Hepatotoxicity can arise as a side effect with these drugs

Tyrosine Kinase Inhibitors

Tyrosine kinases: Family of enzymes involved in cell signaling and growth.
Inhibitors (imatinib): block tyrosine kinase activity, used in cancers involving affected pathways.
Imatinib (Glivec): Used for CML (Philadelphia chromosome-positive) cancers.
Adverse effects : fluid retention and hepatotoxicity.

Monoclonal Antibodies (-MABs)

Monoclonal antibodies are used to target proteins on the surface of cancer cells or immune cells.
They are administered intravenously (IV).

Miscellaneous Agents

Bortezomib: Inhibits cellular proteasomal function, used in multiple myeloma.
Biological response modifiers: Enhance the host's immune response to cancer cells. Interferons are examples.

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Description

Test your knowledge on cancer treatment, focusing on pharmacotherapy and monoclonal antibodies. This quiz covers mechanisms of action, side effects, and the classification of various cancer therapies. Challenge yourself with questions related to Imatinib, Bevacizumab, and combination chemotherapy.