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54 Cards in this Set
- Front
- Back
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What are the treatment strategies for cancer?
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Antineoplastics
Anti-angiogenic drugs Vaccines Immunomodulators |
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What are the rules of Skipper's model of cancer growth? How are they applied to therapy? What types does this model work for?
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Doubling time of cancer cells is constant and number of cells killed during treatment is constant.
Repeated dosing with therapy agents can cure cancer. Works for leukemias |
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What are the rules of the Gompertzian growth model of cancer? How are they applied to therapy?
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Solid tumors consist of proliferating and quiescent cells. The larger the tumor, the lower the percentage of proliferating cells.
A tumor is more likely to be cured when it is small. Increasing drug frequency is more effective than increasing dose. |
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What are the phases of the cell cycle?
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M- phase: mitosis
G1- phase: Cell growth S phase: DNA replication G2- phase: Preparation for mitoss |
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What drugs block the G1 phase? S phase? G2 phase? M phase?
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G1 blocked by cycline dependent kinases.
S phase blocked by DNA synthesis inhibitors (antimetabolites) G2 phase blocked by microtubule and topoisomerase inhibitors M phase blocked by microtubule inhibitors |
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What are the mechanisms of drug resistance (7)?
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Decreased uptake
Increased efflux Modification of targeted enzymes Increased drug metabolism and detoxification Modification of extracellular proteins Increased DNA repair Decreased apoptosis |
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What drugs gain resistance due to decreased uptake?
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Antimetabolites
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What proteins are involved in increased efflux as a mechanism of drug resistance?
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P-glycoprotein
Multidrug resistance proteins |
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What drugs gain resistance due to increased efflux?
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Hydrophobic compounds- anthracyclines, vinca alkaloids, taxanes
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What molecule is increased to cause increased drug metabolism in drug resistance?
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Glutathione
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What drugs gain resistance by increased DNA repair mechanisms?
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Alkylating agents
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What molecule causes decreased apoptosis in drug resistance?
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p53
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What are the principles of the Goldi-Coldman model of combination chemotherapy?
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Different working mechanisms
Non-overlapping toxicities Non-cross-resistance mechanisms |
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What are some of the common side effects of antineoplastics?
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Myelosuppression
Nausea/ vomiting GI tract injury Alopecia Infertility Cardiotoxicity Neurotoxicity Increased risk of secondary cancer |
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What are the results of myelosuppression associated with chemotherapy?
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Higher infection rate
Increased bleeding Anemia |
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Why does nausea and vomiting occur with chemotherapy? What drugs are used to treat it?
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Chemoreceptor trigger zone and vomiting center express receptors that are sensitive to antineoplastics. Also due to GI toxicity.
Metoclopramide- dopamine receptor antagonist Ondansetron and granisetron- Serotonin receptor antagonist |
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What is tumor lysis syndrome? What are symptoms?
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In large or proliferating tumors, rapid cell death after therapy can cause massive release of cellular metabolites.
Hyperuricemia, hyperkalemia, hyperphospatemia, secondary hypocalcemia result. Can result in organ failure and death. |
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Why is angiogenesis a target for cancer treatment?
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Tumors induce angiogenesis by secreting VEGF, FGF, PDGF due to increased need for oxygen and nutrients.
Preventing angiogenesis can limit tumor growth. |
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In what ways to antiangiogenic drugs prevent angiogenesis?
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Block matrix breakdown
Direct inhibition of endothelial cell activation Blockade of angiogenesis activators Inhibition of endothelial-specific integrin/ survival signal |
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What is active cellular immunotherapy? How is it done? Why is it not done often?
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Approach to treat cancer that uses patient's antigen-presenting cells to re-engage the patient's T cells to attack specific cancer.
APCs are removed from the patient, presented to specific antigens and readministered to the patient. ACI is very expensive and not shown to increase survival. |
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What are the classes of antineoplastic drugs?
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Alyklating agents
Antibiotics Antimetabolites Plant alkaloids Hormonal agents Antibodies |
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What is the mechanism for alkylating cancer drugs? What are the side effects?
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Form covalent alkyl bonds with DNA bases, causing cross linking. This inhibits DNA replication.
Myelosuppression, and future cancer can occur. |
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What are types of alkylating cancer drugs?
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Nitrogen mustards- mechlorethamine, cyclophosphamide
Nitrosoureas- carmustine, streptozocin Cisplatin |
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What was the first antineoplastic developed? What are side effects?
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Mechlorethamine
Does not require bioactivation, so causes extravasation reaction and myelosuppression. No longer used. |
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What is the mechanism of cyclophophamide? What is the toxicity? What drug is given to prevent side effects?
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DNA cross-linking, requires bioactivation.
Bladder and renal toxicity, myocarditis, congestive heart failure. Treat renal toxicity with Mesna. |
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What is the mechanism of nitrosoureas? What are they used for?
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Alkylation of DNA and RNA, does not require bioactivation.
Crosses the BBB- brain tumors. |
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What is the mechanism of Carmustine, Lomustine and Semustine? What is the indication?
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DNA cross-linking (nitrosourea)
Primary brain tumors |
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What is the mechanism of Streptozocin? What are the side effects?
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DNA alkylation, but no cross linking
Mild myelosuppression, renal toxicity, diabetes, extravasation injury. |
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What is the mechanism for Cisplatin and Carboplatin? What are the acute, subacute and chronic side effects?
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DNA cross linking
Acute: hypersensitivity, nausea/ vomiting Subacute: renal and gonadal toxicity, myelosuppression Chronic: neurotoxicity, secondary tumors |
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What are the two major mechanisms for antibiotics against cancer?
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DNA cross-linking
Inhibition of DNA topoisomerase |
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What is the mechanism of Actinomycin D? What are the side effects?
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DNA cross linking; inhibition of topoisomerase II.
Myelosuppression, nausea/ vomiting, photosensitivity, radiosensitizer. |
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What is the mechanism for Mitomycin? What are the side effects?
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DNA cross linking and free radical production.
Delayed myelosuppression, renal toxicity, lung fibrosis. |
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What is the mechanism for Bleomycin? What are the side effects?
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DNA cross linking and free radical formation.
Fatal acute allergic reaction, skin and lung toxicity, pulmonary fibrosis, lack of myelosuppression. |
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What is the mechanism for Anthracycline? What are the side effects?
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Inhibition of topoisomerase II and DNA intercalation.
Myelosuppression, severe extravasation injury, serious cardiac toxicity. |
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What is the mechanism of anti-metabolites? What phase of the cell cycle do they work?
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Mimic folic acid, pyrimidine and purine to block enzymatic reactions.
Block the S phase of the cell cycle |
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What is the mechanism of methotrexate? What are the side effects? What drug is given to alleviate these?
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Folic acid analogue that inhibits dihydrofolate reductase.
Myelosuppression, renal damage, liver toxicity. Leucovorin (folinic acid) is used to bypass the folic acid cycle and reduce toxicity. |
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What is the mechanism of 5-fluorouracil? What are the side effects? What deficiency is associated with increased toxicity?
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Pyrimidine analogue that inhibits thymidylate synthase.
Myelosuppression, long term CNS effects, hepatotoxicity, cardiotoxicity, photosesitivity. Dehydropyrimidine dehydrogenase deficiency. |
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What is the mechanism of mercaptopurine? What are the side effects? What deficiency is associated with increased toxicity?
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Purine analogue. Monophosphate inhibits purine synthesis enzymes. Triphosphate causes strand breakage.
Myelosuppression, hepatotoxicity. Thiopurine methyltransferase |
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What drugs affect microtubules? What do they do?
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Vinca alkaloids inhibit microtubule polymerization
Taxanes inhibit microtubule depolymerization |
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What are the side effects of vinblastine? Vincristine?
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Vinblastine- myelosuppression
Vincristine- neurologic toxicity, peripheral neuropathy. |
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What are the side effects of paclitaxel and docetaxel?
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Myelosuppression, type I hypersensitivity, peripheral neuropathy
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What is the mechanism of epidodophyllotoxins (etoposide and teniposide)? What are the side effects?
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Inhibition of topoisomerase II
Myelosuppression, peripheral neuropathy, secondary tumors |
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What is the mechanism of camptothecins (topotecan and irinotecan)? What are the side effects? What deficiency is associated with increased side effects? What is the indication?
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Inhibition of topoisomerase I
Haemorrhagic cystitis, myelosuppression, severe diarrhea. Gilbert's disease Colorectal cancer |
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What is the mechanism of prednisone? What are the long term complications?
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Prevents immune cell proliferation, induces cell death, side effect relief. Mostly synergistic.
Adrenal atrophy- Cushings; immunosuppression, glucose intolerance, osteoporosis, edema, hypertension. |
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What is the mechanism of monoclonal antibodies? what are the side effects?
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Monoclonal IgG antibodies specific to a certain antigen.
Complement mediated cytotoxicity, radioactive molecules deliver drugs, block specific receptor, bind to growth factors. Allergic reaction. |
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What is the antigen for Rituximab? What is the indication?
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CD20 found on B cells
B cell non-Hodgkin's lymphoma |
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What is the antigen for Trastuzumab? What are the side effects? What is the indication?
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Her2/neu
Cardiotoxicity, hypersensitivity. Metastatic breast cancer |
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What is the antigen for Cetuximab? What are the side effects? What is the indication?
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EGFR
Interstitial lung disease, skin reactions. Used with irinotecan in colorectal cancer |
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What is the antigen for Bevacizumab? What are the side effects?
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VEGF
Hypertension, bleeding |
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What is the mechanism of Imatinib? What are the indications? What are the side effects?
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Inhibitor of tyrosine kinase for PDGF, BCF-ABL and c-kit.
Chronic myeloid leukemia, GIST Neutropenia, thrombocytopenia, hepatotoxicity, renal toxicity, muscle cramps, edema. |
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What is the mechanism of Sunitinib? What are the indications? What are the side effects?
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Inhibitor of tyrosine kinase on PDGF, VEGF, c-kit, RTK.
Renal cell carcinoma, GIST Hypertension, skin discoloration |
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What is the mechanism of Gefitinib? What are the indications? What are the side effects?
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EGFR tyrosine kinase blocker
Non small cell lung cancer Fatal interstitial lung disease, bleeding |
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What is the mechanism of Bortezomib? What is the indication? What are the side effects?
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Inhibits the 26S proteasome complex.
Multiple myeloma Asthenia, peripheral neuropathy, myelosuppression, shingles |
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What is the mechanism of Thalidomide? What is the indication? What are the side effects?
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Inhibits TNF alpha
Multiple myeloma Blood clotting, TERATOGENIC |
