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84 Cards in this Set
- Front
- Back
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What are the five major classes of chemotherapeutic agents?
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Alkylating Agents
Antimetabolites Plant Derivatives Antibiotics Hormones |
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Are tumors with high or low growth factors most sensitive to chemo?
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High
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Does growth fraction increase or decrease with size of tumor?
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Decrease
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Is the growth fraction increased or decreased by surgery and radiation?
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Increased
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Do tumor populations become more or less heterogeneous with time?
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More heterogeneous, which increases the chances of occurance of drug-resistant cell variants
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Why is interval treatment done in chemo?
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To allow bone marrow recovery and minimize normal cell toxicity
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What can be given to a patient to potentially reduce neutropenia associated with chemotherapy?
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G-CSF (primarily used in chemo)
GM-CSF (primarily used in transplantation) |
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What can be given to a patient to help alleviate the nausea and vomiting commonly associated with chemotherapy?
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5-HT (seratonin) antagonists (ondansetron)
D2-receptor antagonists (prochlorperazine and metoclopramide) |
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What two anticancer drugs cause cardiac toxicity?
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Doxorubicin
Daunorubicin (both anthracyclines) |
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Which two anticancer drugs cause nervous system toxicity?
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Vincristine
Vinblastine (both vinca alkaloids) |
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Which anticancer drug causes pulmonary toxicity?
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Bleomycin
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Which anticancer drug causes urinary tract toxicity?
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Cisplatin
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Which anticancer drug causes hypersensitivity reactions?
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L-asparaginase
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True of False: Anticancer drugs have the narrowest therapeutic index in all of medicine.
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TRUE
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What are the four mechanisms of drug resistance in tumor cells?
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1. Decreased concentration of drugs in cells
2. Decreased levels of active drug in cell 3. Altering the target 4. Repair of damage |
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What is the largest class of anticancer drugs?
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Alkylating agents
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What is the mechanism of alkylating agents?
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Cause DNA damage by causing DNA cross-linking
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Are alkylating agents CCNS or CCS?
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CCNS
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What are the mechanisms of tumor resistance to alkylating agents? (3)
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1. Increased capability to repair DNA
2. Decreased permeability of drug 3. Increased production of glutathione |
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What are the five groups of alkylating agents?
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Nitrogen mustards
Alkylsulfonates Ethylenimines Nitosureas Triazenes |
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Name three nitrogen mustards.
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Cyclophosphamide
Methchlorethamine Chorambucil |
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What is the most widely used alkylating agent?
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Cyclophosphamide
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True or false: Cyclophosphamide is a prodrug that requires conversion by hepatic cytochorome P450.
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TRUE
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Name three nitrosoureas?
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Carmustine
Lomustine Semustine |
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True or False: Nondividing cells will always be killed by nitrosureas, regardless of DNA repair activity of the cells.
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FALSE
"cytotoxicity is see only upon cell division, therefore nondividing cells can escape death if DNA repair occurs" |
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Why are nitrosureas commonly used in the treatment of brain tumors?
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Because they can penetrate the CNS
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Cisplatin is most toxic at which phases of the cell cycle?
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G1 and S
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What is the major toxicity of cisplatin?
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Neprotoxicity
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What can be used in place of cisplatin in order to avoid that drug's nephrotoxicity?
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Carboplatin
(is myelosuppressive, however) |
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What is the major limitation to successful treatment with cisplatin?
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Resistance
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Are antimetabolites CCS or CCNS?
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CCS
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What is the major toxicity of antimetabolites?
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Myelosuppression
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What is the most commonly used folate analog?
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Methotrexate
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Folate analogs lead to the depressed synthesis of what?
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DNA
RNA Proteins |
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What is the mechanism of methotrexate (folate analog)?
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Blocks DHFR
(enzyme that converts folic acid into its active form) |
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What are the mechanisms of resistance for folate analogs? (3)
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1. Increased DHFR levels
2. Mutant DHFR with decreased drug binding 3. Decreased uptake |
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What are the commonly used purine analogs?
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6-mercaptopurine
6-thioguanine |
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What are the two mechanisms of purine analogs?
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Block enzymes involved in purine synthesis
Are incorporated into RNA and DNA, leading to damage |
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What is the most common mechanism of resistance to purine analogs?
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Decreased HGPRT activity
(enzyme that converts analogs into unnatrual nucleotides) |
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Name four pyramadine analogs.
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5-fluorouracil
Cytarabine Gemicitabine Capecitabine (oral 5-FU) |
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True or false: 5-FU requires intracellular activation to its activated form.
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TRUE
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What are the two mechanisms of 5-FU?
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Inhibits thymidylate synthase → inibits DNA synthesis
Incorporated (5-FUTP) into RNA |
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What is the mechanism of cytarabine?
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Competitive inhibition of DNA polymerase
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What is the mechanism of resistance to cytarabine?
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Depletion of activating enzyme deoxycytidine kinase
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What is the common mechanism of resistance to plant derivate chemo agents?
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P-glycoprotein upregulation
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What phase of the cell cycle are vinca alkaloids specific to?
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M
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What is the mechanism of vincristine and vinblastine?
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Prevent polymerization of tubulin to form microtubules, thus inhibiting mitosis
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What is the dose-limiting toxicity for vinblastine and vincristine?
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Vinblastine = myelosuppression
Vincristine = peripheral neuropathy |
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What is the mechanism of resistnace to the vinca alkaloids?
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Decreased uptake and retention (MDR)
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What are the two podophyllotoxins we need to know?
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Etoposide
Teniposide |
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What is the target of etoposide?
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Topoisomerase II
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Is etoposide CCS or CCNS?
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CCS
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What is the mechanism of resistance to etoposide?
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Decreased accumulation (MDR)
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What is the mechanism of action of taxanes?
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Promote tubulin polymerization and stabalization → cells become frozen in mitosis
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Which antibiotic is CCS?
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Bleomycin
(all others CCNS) |
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At which phases do doxorubicin and daunorubicin have maximal activity?
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S and G2
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What is the mechanism of cardiac toxicity by antracycline antibiotics?
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Oxygen radical formation
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What is the most important mechanism of anthracycline antibiotics?
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Formation of covalent topo II-DNA complexes to prevent religation
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What is the mechanism of resistnace to doxorubicin?
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Increased efflux
MDR |
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What is the mechanism for actinomycin?
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Intercalation into DNA
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What phase does bleomycin cause cells to accumulate in?
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G2
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What is the mechanism of bleomycin?
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Production of single- and double-strand DNA breaks that result from the production of free radicals
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What is the primary toxicity of bleomycin?
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Pulmonary toxicity
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Name four antiestrogens.
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Tamoxifen
Anastrazole (aromatase inhibitor) Exemestane Letrozole |
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How does the affinity of tamoxifen for the ER compare to that of estrogen?
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Affinity is 10-fold lower
Estrogen ablation still required |
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What is the most prominent side-effect of tamoxifen?
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3-fold increase in potential for endometrial cancer
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What is the primary use of tamoxifen?
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As adjuvant therapy after surgery for breast CA
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Name two gonadatropin-releasing hormone agonists.
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Leuprolide
Goserelin |
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Is testicular andgrogen synthesis increased or decreased by treatment with GnRH agonists?
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Decreased
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Is release of follicle-stimulating hormone and leutenizing hormone stimulated or inhibited by GnRH agonists?
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Inhibited
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Does prednisone require activation?
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Yes
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What is the mechanism of hydroxyurea?
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Inhibition of the enzyme ribonucleotide reductase
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Is hydroxyurea phase specific?
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Yes - S phase
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What is the mechanism of L-Asparaginase?
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Catalyzes deamination of extracellular asparagine, which some tumor cells can't make on their own (ALL)
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Does L-asparaginase induce myelosuppression?
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No
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What is the mechanism of resistance to L-Asparaginase?
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Increased expression of asparagine synthetase gene
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Trestuzumab (Herceptin) is used in the treatment of what?
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Inhibitor of HER2 in breast cancer
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Cetuximab (Erbitux) is used in the treatment of what?
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Inhibitor of EGFR in colorectal cancer
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Bevacizumab (Avastin) is used in the treatment of what?
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Inhibitor of VEGF in colorectal cancer
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Gefitinib is used in the treatment of what?
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Inhibitor of EGFR in non-small cell lung cancer
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Imatinib (Gleevec) is used in the treatment of what?
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Inhibitor of Bcr-Abl in CML
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Erlotinib is used in the treatment of what?
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Inhibitor of EGFR in non-small cell lung cancer
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Name three monoclonal antibodies used as anticancer drugs?
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Trastuzumab
Cetuximab Bevacizumab |
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Name two kinase inhibitors that inhibit EGFR.
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Gefitinib
Erlotinib |
