Anticancer Drugs
83 Questions
18 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the role of dihydropyrimidine dehydrogenase (DPD) in the context of 5-fluorouracil therapy?

  • DPD enhances the drug's efficacy by increasing its concentration
  • DPD facilitates the absorption of 5-fluorouracil in the gastrointestinal tract
  • DPD is essential for the biotransformation of fluoropyrimidines (correct)
  • DPD inactivates fluoropyrimidines to reduce side effects

    • What was the primary cause of cancer identified by Percival Pott in chimney sweepers?

  • Exposure to coal tar soot (correct)
  • Inadequate nutrition
  • Poor hygiene practices
  • Genetic predisposition

    • In the case study, what potential genetic factor could explain the severe toxicity experienced by the patient?

  • Variations in the CYP450 enzyme system
  • Mutations in the p53 gene
  • Increased expression of tumor necrosis factor
  • Genetic polymorphisms in dihydropyrimidine dehydrogenase (correct)

    • What is the role of anticancer drugs in terms of cell population reduction?

    <p>They kill a constant proportion of cells regardless of population size.</p> Signup and view all the answers

    Which chemotherapy approach is primarily used for localized cancers?

    <p>Neoadjuvant Chemotherapy</p> Signup and view all the answers

    What is an effect of drug combinations in cancer chemotherapy?

    <p>They can reduce the likelihood of drug resistance.</p> Signup and view all the answers

    Which of the following is NOT a mechanism of resistance to anticancer drugs?

    <p>Decreased production of metabolic enzymes</p> Signup and view all the answers

    Which phase of the cell cycle is primarily affected by antimetabolites?

    <p>S phase</p> Signup and view all the answers

    Which of the following therapeutic approaches is most common in cancer treatment?

    <p>Adjuvant Chemotherapy</p> Signup and view all the answers

    Which type of cancer is chemotherapy most effectively combined with as a primary induction?

    <p>Hodgkins lymphoma</p> Signup and view all the answers

    What is one mechanism of drug resistance relating to altered target enzymes?

    <p>Enzyme target becomes less sensitive to drug’s inhibition</p> Signup and view all the answers

    Which of the following describes a common property of alkylating agents?

    <p>Alkylate DNA bases causing cross-links</p> Signup and view all the answers

    What is MAO of Cyclophosphamide as an anticancer drug?

    <p>Gives up its alkyl group to DNA and stops cell replication</p> Signup and view all the answers

    What happens during the formation of trapping agents in relation to anticancer drugs?

    <p>They bind to and neutralize the drug.</p> Signup and view all the answers

    Which of the following factors contributes to decreased drug accumulation in resistant cancer cells?

    <p>Increased expression of multi-drug transporters</p> Signup and view all the answers

    Which modification might protect cells from the effects of purine antimetabolites?

    <p>Decreased activation of prodrugs due to enzyme activity changes</p> Signup and view all the answers

    What is the primary mechanism of action of procarbazine in cancer treatment?

    <p>It generates hydrogen peroxide leading to DNA strand scission.</p> Signup and view all the answers

    Which of the following drugs is considered a direct-acting alkylating agent?

    <p>Cisplatin</p> Signup and view all the answers

    What is one of the major adverse drug reactions (ADRs) associated with cisplatin?

    <p>Nephrotoxicity</p> Signup and view all the answers

    Which of these antimetabolite drugs specifically antagonizes folic acid?

    <p>Methotrexate</p> Signup and view all the answers

    During cancer chemotherapy, which mechanism is not attributed to traditional alkylating agents?

    <p>Inhibition of RNA transcription</p> Signup and view all the answers

    In the ABVD-MOPP regimen, which drug is NOT included?

    <p>Methotrexate</p> Signup and view all the answers

    What is a common side effect of procarbazine when used in chemotherapy?

    <p>Peripheral neuritis</p> Signup and view all the answers

    Which of the following cancer types is NOT typically treated with alkylating agents?

    <p>Prostate cancer</p> Signup and view all the answers

    What term describes the uncontrolled growth of cells that often invades healthy tissue?

    <p>Neoplasia</p> Signup and view all the answers

    What does the prefix 'onco-' refer to?

    <p>Swelling or mass</p> Signup and view all the answers

    What common name is given to a condition related to chimney sweeps caused by soot exposure?

    <p>Soot wart</p> Signup and view all the answers

    Which term is used to describe a gene that can induce a cell to become malignant?

    <p>Oncogene</p> Signup and view all the answers

    What is one of the major functions of laboratory testing for tumor markers?

    <p>Classification (staging)</p> Signup and view all the answers

    Which type of tumor marker is Prostate Specific Antigen (PSA)?

    <p>Enzyme</p> Signup and view all the answers

    When are elevated levels of Human Chorionic Gonadotropin (hCG) typically found?

    <p>In pregnancy and germ cell tumors</p> Signup and view all the answers

    Which of the following is an application of tumor markers in clinical practice?

    <p>Estimation of tumor volume</p> Signup and view all the answers

    Alpha-fetoprotein (AFP) serves as a marker for which type of cancers?

    <p>Liver and germ cell carcinoma</p> Signup and view all the answers

    What does an increase in CEA levels indicate?

    <p>Possible recurrence of colorectal and other associated cancers</p> Signup and view all the answers

    What characterizes the genes related to the return of high levels of oncofetal proteins later in life?

    <p>They are suspected to be reactivated as a potential initial step in cancer formation</p> Signup and view all the answers

    What is the mechanism of action (MOA) of paclitaxel?

    <p>Disrupts microtubule function</p> Signup and view all the answers

    What tree is paclitaxel derived from?

    <p>Pacific yew tree</p> Signup and view all the answers

    What are the common adverse drug reactions (ADRs) of paclitaxel?

    <p>Myelosuppression, peripheral sensory neuropathy</p> Signup and view all the answers

    What is the mechanism of action (MOA) of cisplatin agents used to treat cancer?

    <p>Binds to DNA and inhibits synthesis</p> Signup and view all the answers

    What is the mechanism of action (MOA) of promethazine?

    <p>Histamine H1 receptor antagonist</p> Signup and view all the answers

    What is hydrocodone-acetaminophen?

    <p>A pain relief medication</p> Signup and view all the answers

    What is the role of microtubules in the cell?

    <p>They provide structural support and shape to the cell.</p> Signup and view all the answers

    Match each item to its description

    <p>alkylating agents = nitrogen mustards, attack cell DNA antimetabolites = block folic acid or purine or pyrimidine in the cancer cells hormonal agents = drugs that block hormones (estrogen, testosterone etc.) required for cancer cell division pathway-targeted drugs = the use of monoclonal antibodies (all end in “mab”) or proteins (all end in “ib”) that target a specific pathway</p> Signup and view all the answers

    Which of the following alkylating agents is not a nitrogen mustard?

    <p>cisplatin</p> Signup and view all the answers

    Match each antimetabolite to its group

    <h1>Folic Acid Inhibitors = methotrexate, leucovorin Purine Inhibitors = mercaptopurine, thioguanine Pyrimidine Inhibitors = capecitabine, fluorouracil</h1> Signup and view all the answers

    Which of the following antibiotics is an anthracycline?

    <p>doxorubicin</p> Signup and view all the answers

    Which of the following natural products are vinca alkaloids?

    <p>vinblastine</p> Signup and view all the answers

    Which of the following drugs is a cytotoxic drug that is also an alkylating agent?

    <p>Procarbazine</p> Signup and view all the answers

    Match each hormonal agent to its group

    <p>Aromatase Inhibitors = anastrozole, formestane Gonadotropin Releasing Hormone Agents = abarelix, leuprolide, goserelin Androgen Receptor Antagonists = bicalutamide Androgen Synthesis Inhibitor = ketoconazole</p> Signup and view all the answers

    Which hormonal agent is an antiestrogen?

    <p>tamoxifen</p> Signup and view all the answers

    Match each to its group

    <p>Epidermal Growth Factor Receptor Inhibitors = cetuximab, panitumumab Kinase Inhibitors = ruxolitinib, cabozantinib Angiogenesis Inhibitors = bevacizumab Tumor Markers = PSA, hCG, AFP, CEA, CA, 125</p> Signup and view all the answers

    Match each treatment modality to when it would be utilized

    <p>surgery and/or radiotherapy = when tumor is localized primary chemotherapy = when widespread distribution neoadjuvant chemotherapy = to reduce localized tumor size so that surgery is more successful adjuvant chemotherapy = used after surgery to prevent recurrence</p> Signup and view all the answers

    When is the use of drug combinations most effective?

    <p>When tumor has a heterogeneous population of genetically different cells</p> Signup and view all the answers

    What is a mechanism of resistance (MOR) for cyclophosphamide?

    <p>Increase expression of DNA repair enzymes</p> Signup and view all the answers

    Which of the following is not an adverse drug reaction (ADR) of cyclophosphamide?

    <p>Hemolysis</p> Signup and view all the answers

    What is cisplatin an analog of?

    <p>Platinum</p> Signup and view all the answers

    What is the mechanism of action (MOA) of cisplatin?

    <p>binds to DNA and inhibits synthesis</p> Signup and view all the answers

    What is cisplatin eliminated by?

    <p>Kidney</p> Signup and view all the answers

    Dose adjustment for creatinine clearance is required for cisplatin.

    <p>True</p> Signup and view all the answers

    Cisplatin is active against a narrow range of cancers

    <p>False</p> Signup and view all the answers

    Which cancer is procarbazine mostly used for?

    <p>Hodgkin’s lymphoma</p> Signup and view all the answers

    What are some ADRs of procarbazine?

    <p>skin reactions</p> Signup and view all the answers

    What is the mechanism of action (MOA) of methotrexate?

    <p>Inhibits human dihydrofolate reductase which blocks synthesis of bases required to make DNA, cell division stops</p> Signup and view all the answers

    What is the antidote for methotrexate?

    <p>Leucovorin</p> Signup and view all the answers

    What is leucovorin?

    <p>Active form of folic acid</p> Signup and view all the answers

    What is the main adverse drug reaction (ADR) for methotrexate?

    <p>Myelosuppression</p> Signup and view all the answers

    What is 6-Mercaptopurine?

    <p>A thiopurine analog, activated to the active monophosphate which inhibits numerous steps in DNA synthesis</p> Signup and view all the answers

    What is the mechanism of action (MOA) for 5-Fluorouracil (5-FU)?

    <p>Converted in the cell to active drugs which inhibits thymidine synthase and leads to cell death</p> Signup and view all the answers

    What is the mechanism of action (MOA) for Vinblastine?

    <p>inhibits microtubule formation in cells, division stops</p> Signup and view all the answers

    What are some adverse drug reactions (ADRs) of vinblastine?

    <p>myelosuppression</p> Signup and view all the answers

    What is the mechanism of action (MOA) for bleomycin?

    <p>binds DNA, forms free radicals and DNA strand breaks occur</p> Signup and view all the answers

    What is bleomycin classified as?

    <p>Antitumor antibiotic</p> Signup and view all the answers

    Which of the following is an adverse drug reaction (ADR) of bleomycin?

    <p>Pulmonary toxicity</p> Signup and view all the answers

    Which of the following best describes a monoclonal antibody?

    <p>Made in mice, all end in 'mab'</p> Signup and view all the answers

    Which of the following describes fusion proteins?

    <p>Not antibodies but proteins made (designed) to bind to specific targets. All end in 'nib.'</p> Signup and view all the answers

    Which of the following fits the description below:

    • MOA: drug inhibits a tyrosine kinase that prevents phosphorylation by ATP of critical proteins
    • Used to treat myelogenous leukemia (CML)
    • Oral dosing
    • ADRs: edema, congestive heart failure?

    <p>Imatinib</p> Signup and view all the answers

    Which of the following is described below:

    • a monoclonal antibody
    • MOA: binds to the EGF receptor and blocks EGF actions, blocks angiogenesis
    • ADRs: skin reactions?

    <p>Cetuximab</p> Signup and view all the answers

    What is the purpose of tamoxifen?

    <p>Estrogen receptor blocker for use in patients with an estrogen positive breast tumor</p> Signup and view all the answers

    Match each cell cycle phase to its description

    <p>G0 = resting phase (many anticancer drugs act on this phase) G1 = components needed for DNA synthesis prepared here S phase = DNA synthesis G2 phase = synthesis of components needed for mitosis</p> Signup and view all the answers

    Match each cell cycle step to the drugs that affect it

    <h1>S Phase = antimetabolites; podophyllotoxins G2 Phase = podophyllotoxins, bleomycin M Phase = vinca alkaloids</h1> Signup and view all the answers

    Match each MOR to the drugs it can affect

    <p>Increased DNA repair = cisplatin and most alkylating agents Formation of trapping agents = bleomycin, cisplatin, anthracyclines Change in target enzymes = methotrexate Decreased activation of prodrug/ Inactivation of drug = purine antimetabolites (mercaptopurine, thioguanine) and the pyrimidine antimetabolites (cytarabine, fluorouracil)</p> Signup and view all the answers

    Which drug class is cell cycle non-specific?

    <p>Alkylating Agents</p> Signup and view all the answers

    What drug is used to treat chronic myelogenous leukemia (CML)?

    <p>Imatinib</p> Signup and view all the answers

    Study Notes

    Cancer Chemotherapy

    • Case Study: A 55-year-old man with colorectal cancer (CRC) and 5 positive lymph nodes had surgery. Treatment with 5-fluorouracil, leucovorin, and oxaliplatin resulted in severe toxicity including myelosuppression, diarrhea, and altered mental state.
    • Fluoropyrimidines: Require dihydropyrimidine dehydrogenase (DPD) for biotransformation. Genetic polymorphisms in DPD can alter biotransformation, possibly explaining the toxicity.
    • Percival Pott (1714-1788): A London physician who described and treated compound fractures of the lower fibula and medial malleolus of the tibia with foot dislocation (Pott's Fracture).
    • Chimney Sweepers: In 1700, coal was the primary heating source. Narrow chimney flues needed annual cleaning. Young boys were hired to clean the flues.
    • Pott (1775): Found cancer of the scrotum in boys (aged 10-14) who worked as chimney sweeps, but not in age-matched controls who lived outside of London. He established a link between the workplace and cancer (tar soot, benzo pyrene).
    • Terms:
      • Cancer: Uncontrolled growth of cells, often with invasion into healthy tissues.
      • Malignant: Disease tending towards death.
      • Neoplasia: Formation of tissue.
      • Neoplasm: New or abnormal formation of tissue.
      • Tumor: Swelling.
      • Onco-: Gr. Onkos, bulk or mass.
      • Oncogene: A gene that can induce a cell to become malignant.

    Theories of Cancer Causes

    • Environmental Exposure: Ionizing radiation.
    • Chemical Carcinogen: Azo dyes, aflatoxins, asbestos, tobacco.
    • Viruses: Human papillomavirus.

    Treatment Modalities

    • Chemotherapy Alone: Cures only about 10–15% of cancers.
    • Increased Cure Rates Require: Surgery, radiation, and chemotherapy.

    Treatment Modalities (Further details)

    • 1. Primary Induction Chemotherapy: For widespread systemic diseases like Hodgkin's lymphoma.
    • 2. Neoadjuvant Chemotherapy: For localized cancers such as breast, bladder cancer, etc.
    • 3. Adjuvant Chemotherapy: Used along with surgery and radiation. This is a common treatment.

    Anticancer Drugs

    • Action: Can act on cells during cell cycling or in the resting phase.
    • Kinetics: Follow first-order kinetics (kill a constant proportion of cells, instead of a constant number).
    • Dosing: Based on log kill function. A 3-log dose decreases cell population from 1012 to 109 cells.
    • Examples: cyclophosphamide, cisplatin, methotrexate, leucovorin, mercaptopurine, vinblastine, paclitaxel, bleomycin, imatinib, cetuximab, tamoxifen, fluorouracil, procarbazine.

    Cell Cycles

    • G0: Resting phase (many anticancer drugs).
    • G1: Synthesis phase, components for DNA synthesis.
    • S: DNA synthesis.
    • G2: Synthesis of components for mitosis.
    • M: Mitosis.

    Cell Cycle Specific Drugs

    • Examples:
      • Antimetabolites
      • Podophyllotoxins
      • Bleomycin
      • Vinca alkaloids.

    Non-Cell Cycle Specific Drugs:

    • Act in resting (G0) and all other phases.

    Drug Combinations

    • (a) Maximize cell kill.
    • (b) Increase coverage for heterogeneous tumor types.
    • (c) Slow or prevent drug resistance (same as antibiotic chemotherapy).

    Mechanisms of Resistance

    • 1. Increased DNA Repair: (cisplatin and most alkylating agents).
    • 2. Formation of Trapping Agents: Increased glutathione synthesis (binds to anticancer drugs).
    • 3. Change in Target Enzymes: Enzyme target becomes less sensitive to drug inhibition.
    • 4. Decreased Activation of Prodrugs: Decreased activity of enzymes to convert prodrugs to active drugs.
    • 5. Inactivation of Drugs: Increased activity of drug inactivating enzymes.
    • 6. Decreased Drug Accumulation: Increased expression of multi-drug transporter (MDR).

    Alkylating Agents

    • Target: DNA, intercalate with DNA and lead to cell death.

    • Examples: cyclophosphamide, nitrogen mustards (chlorambucil, mechlorethamine), nitrosoureas (carmustine, lomustine), alkyl sulfonates (busulfan), cisplatin, procarbazine.

      • Resistance: Increased expression of DNA repair enzymes. Reduced drug transport into the cell. Increase glutathione levels.

    • Mechanism of Action: Direct-acting on DNA; Phase I CYP450 required for activation of some to a metabolite (e.g. cyclophosphamide).

    • Wide range of Clinical uses: breast, ovarian, neuroblastomas, bladder etc.

    Cisplatin

    • Inorganic platinum analog.
    • Binding to DNA blocks replication.
    • Adverse drug reactions (ADRs): nausea, vomiting, peripheral neuropathy, nephrotoxicity, ototoxicity, etc.
    • Free radical generation: Procarbazine forms hydrogen peroxide which causes free radicals, resulting in DNA strand scission.

    Procarbazine

    • Orally active with wide tissue distribution.
    • Alkylating agent with a different MOA.
    • Used primarily for Hodgkin's Disease
    • Major ADRs: Myelosuppressant, GI irritant, CNS dysfunction, peripheral neuropathy, skin reactions.

    Antimetabolites

    • Drugs are cell cycle-specific inhibitors.
    • Resemble endogenous compounds, acting as antagonists to systems that use those compounds.
    • All are antagonists of either folic acid (methotrexate), purines (mercaptopurines, thioguanine), or pyrimidines (fluorouracil, cytarabine).

    Methotrexate

    • Inhibits dihydrofolate reductase (an enzyme that activates folate).
    • Antimetabolite acting as a sulfa drug.
    • Blocks folate synthesis in cancer cells (and other cells).
    • Resistance: Reduced drug transport into the cell. Decreasing cytotoxic drug metabolites. Increasing expression of reductase enzyme. Decreasing enzyme affinity.

    Leucovorin

    • Rescue drug given with high dose methotrexate to reduce toxicity (myelosuppression).

    Mercaptopurine (6-MP)

    • Purine antimetabolite activated by hypoxanthine-guanine phosphoribosyltransferase (to toxic nucleotide).
    • Inhibits enzymes involved in purine metabolism.
    • A thiopurine analog that needs activation to a monophosphate form.

    Fluorouracil (5-FU)

    • Converted into a metabolite that inhibits thymidylate synthase, causing cell death.

    Plant Alkaloids

    • Cell-cycle selective drugs.
    • Vinca alkaloids (vinblastine) block mitotic spindle formation by preventing tubulin dimers in microtubules.
    • Taxanes (paclitaxel) block mitotic spindle through inhibition of microtubule disassembly into tubulin monomers.

    Bleomycin

    • Cell cycle-selective (G2 phase) drug.
    • Generates free radicals and causes DNA strand breaks.

    Hormonal Agents

    • Certain cancers require steroid hormones for continued growth. Tumors produce receptors for steroids. Measuring estrogen and progesterone receptors is standard practice. Hormone therapy is not effective on ER/PR receptor-negative cancers.

    Tamoxifen

    • Drug is an antagonist at estrogen receptors on tumors.

    Enzyme Inhibitors and Antibodies

    • A wide range of drugs, targeting enzymes and metabolic pathways to shut down cancer cell growth.

    Imatinib

    • Inhibitor of tyrosine kinase.
    • Prevents phosphorylation and activation of the Bcr-Abl oncogene.
    • Used in the treatment of chronic myelogenous leukemia.

    Growth Factor Receptor Inhibitors

    • Many solid tumors overexpress epidermal growth factor receptors (EGFR).
    • Blocking these receptors prevents angiogenesis.
    • Examples include Cetuximab (a monoclonal antibody).

    Cancer Chemotherapy: Drug Selection

    • Only active against cancer cells.
    • Different mechanisms of action for combined drugs.
    • Minimal cross-resistance.
    • Different toxic effects to avoid cumulative effects.

    Cancer Chemotherapy: Drug Usage

    • Pulse therapy: High doses for short periods (to allow the body to recover).
    • Recruitment: Cell cycle-selective drugs cause increased levels of cell death and recruit resting cells into cell division (to target actively dividing cells).
    • Synchrony: Use drugs to stop cells in M or S phase.
    • Rescue Therapy: Reverse side effects of anticancer drugs using drugs like leucovorin (rescuing cells by providing target of the toxic agent given earlier).

    The First Tumor Marker (1846)

    • Bence Jones proteins in urine precipitate (in acidic solutions).
    • Now recognized as light chains from immunoglobulins overproduction by plasma cells (multiple myeloma).

    Tumor Markers

    • Substances present in or produced by tumors or the host in response to tumors.
    • Used to determine tumor presence in blood or secretions.
    • Tumors resemble fetal tissues morphologically.

    Tumors

    • Graded based on differentiation: Well-, poorly differentiated, and anaplastic.
    • Tumor markers are re-expressions of substances produced by embryogenically related tissues.

    Tumor Markers Classification

    • Enzymes: Catalytic activity vs. mass.
    • Hormones: Immunoassay.
    • Oncofetal Antigens: AFP, CEA, PSA.
    • Tumor Antigen Cell Surface Markers: CA 125, CA 15-3, CA 19-9.

    Applications of Tumor Markers

    • Screening general population.
    • Differential diagnosis in symptomatic patients.
    • Clinical staging in cancer.
    • Estimating tumor volume.
    • Evaluating treatment outcomes.
    • Detecting recurrence.
    • Monitoring therapy response.
    • Guiding immunotherapy.

    Prostate-Specific Antigen (PSA)

    • Protease enzyme found in prostate tissue.
    • Discovered in 1971.
    • MW 28,430 single chain glycoprotein.
    • Bound and free forms in serum.

    Human Chorionic Gonadotropin (hCG)

    • Glycoprotein produced by the placenta.
    • Used for pregnancy detection.
    • Alpha and beta subunits.
    • Elevated levels can indicate germ cell tumors.

    Oncofetal Proteins

    • Proteins produced in normal fetal tissues, elevated levels in later life suggest reactivated genes.
    • Alpha feto protein (AFP), carcinoembryonic antigen (CEA)
    • Levels are high at birth and decline. Elevated levels later in life can indicate cancer development.

    Alpha-fetoprotein (AFP)

    • Liver and germ cell carcinoma marker.
    • Glycoprotein, single polypeptide chain.
    • High levels at birth, lower in adults.
    • Elevated levels can indicate incomplete tumor removal after surgery (liver tumor).

    Carcinoembryonic Antigen (CEA)

    • Marker for colorectal, GI, lung and breast cancers.
    • Single glycoprotein polypeptide chain.
    • Elevated levels in many non-cancer conditions.
    • Primarily used to monitor therapy and recurrence.

    Carbohydrate Markers

    • Either antigens on tumor cell surfaces or secreted by the tumor cell.
    • Tend to be more specific than hormones or enzymes.
    • Examples include CA 15-3, CA 549, CA 19-9, CA 19-5, CA 72-4, and CA 50.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Related Documents

    PM 716 C54 Anticancer Slides PDF

    Description

    This quiz explores the roles of dihydropyrimidine dehydrogenase and the adverse effects related to 5-fluorouracil therapy. Additionally, it examines historical cancer causes identified by Percival Pott and the genetic factors that may influence chemotherapy toxicity. Test your knowledge on these critical oncology concepts!

    More Like This

    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser