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78 Cards in this Set
- Front
- Back
- 3rd side (hint)
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What sort of drug is cyclophosphamide?
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nitrogen mustard
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Describe the process of activation of cyclophosphamide.
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p450 -> adds active alkyl groups
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How does activated cyclophosphamide work?
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Active alkyl groups bind 2 DNA strands.
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How broad of a clinical spectrum does cyclophosphamide cover. Examples? (2)
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CLL and many solid tumors
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What nitrosoureas are used as chemotherapeutics? (3)
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Carmustine
Lomustine Streptozocin |
Musty, not musty
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How are nitrosoureas activated?
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Non-enzymatic (ie, spontaneous breakdown)
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What are the activated forms of nitrosoureas?
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1) reactive alkylating agents
2) Isothiocyanate -> modifies protein, especially DNA repair enzymes -> impared DNA repair |
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Which nitrosoureas are myelosuppressive?
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Carmustine
Lomustine Streptozocin is NOT myelosuppresive |
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Which nitrosoureas are lipid soluble?
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Carmustine
Lomustine |
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Which nitrosoureas are used to treat primary brain tumors?
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Carmustine
Lomustine |
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Which nitrosourea is used to treat insulinomas? Why?
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Streptozocin -> glucose analogue -> high affinity for GLUT-2 transporter on islet cells
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How does cisplatin work?
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Like alkylating agents, it cross-links DNA. However, cisplatin is NOT an alkylating agent.
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What is the main side effect of cisplatin?
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nephrotoxity -> slowly reversible, controlled by hydration and diuresis
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What is cisplatin used for?
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IT IS A FIRST LINE DRUG FOR MANY SOLID TUMORS.
Useful in treating melanoma. |
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What enzyme does MTX interfere with?
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DHFR
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What cellular processes does MTX interfere with? (2)
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1) Inhibits conversion from dUMP to dTMP.
2) Inhibits DE NOVO purine ring synthesis, due to lack of a 1-carbon donor. |
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What are the main side effects of MTX?
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1) Bone marrow suppression
2) Mucosal ulceration |
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What is the antidote for MTX overdose?
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Leucovorin (folinic acid)
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How does MTX accumulate inside cells?
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It is ACTIVELY TRANSPORTED into cells, then POLYGLUTAMATED.
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What are the main mechanisms of MTX resistance? (3)
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1) Block transport
2) Block polyglutamation 3) Overexpress DHFR |
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What are the two metabolites of fluorouracil? How do they interfere with cancer?
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F-dUMP -> inhibits thymidylate synthase
F-UTP -> interferes with RNA synthesis |
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What is the exclusive use of fluorouracil?
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Exclusively used for SOLID TUMORS, most notable example is actinic keratoses
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What is the most important antimetabolite drug for the treatment of AML?
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Cytarabine
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Which leukemia is associated with the philadelphia chromosome?
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CML
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What are the main side effects of 5-FU? (2)
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1) Myelosupression
2) Mucosal damage |
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A 45 yo man is diagnosed with AML. He is treated with two antimetabolite drugs, one for induction and one for maintenance. What are they?
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Induction: cytarabine
Maintenance: 6-thioguanine |
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What drug is used for the maintenance of ALL?
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6-Mercaptopurine
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What is 6-mercaptopurine an analogue of?
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hypoxanthine
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What was the first agent used to "cure" a cancer? Which cancer?
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MTX -> choriocarcinoma
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You learned one drugs for the maintenance of ALL and one for the maintenance of AML. What are they?
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ALL: 6-mercaptopurine
AML: 6-thioguanine |
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How do anthracyclines work? (3)
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1) Most important: inhibits topoisomerase II
2)Intercalating agent 3) Quinone moieties -> free radicals |
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What is the suffix of anthracyclines?
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-rubicin
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What are the 2 anthracyclines that we learned?
Which one is broad spectrum, and which one is narrow spectrum? |
Narrow spectrum: daunorubicin
Broad specturm: doxorubicin |
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What is the primary use of daunorubicin?
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non-lymphoytic leukemias
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What is the most important side effect of the anthracyclines?
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Cumulative, dose-related cardiac damage.
Also causes total hair loss |
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Which drug is the best antimetabolite for most breast cancers?
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Doxorubicin
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How does bleomycin work?
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Bleomycin binds iron -> forms psudoenzyme -> generates free radicals -> fragments DNA
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What stage of the cell cycle does bleomycin work best in?
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Bleomycin works best in G2, but actually works in all the phases even in non-dividing cells (ie, G0)
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How broad of a spectrum does bleomycin have?
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Very broad
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What is the main toxicity of bleomycin?
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Pulmonary fibrosis.
FYI, bleomycin does NOT cause myelosuppression |
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How do vinca alkaloids work?
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Bind to tubulin monomers, preventing polymerization.
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What is the difference between taxol and the vince alkaloids?
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Taxol -> binds tubulin polymers -> prevents depolymerization
Vinca alkaloids -> bind tubulin monomers -> prevent polymerization |
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What is the one thing that vinca alkaloids and taxol have in common?
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Both act exclusively on the M phase, because mitosis is the point in the cell cycle most dependent on microtubule fxn.
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What are the two vinca alkaloids that we learned?
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Vincristine
Vinblastine |
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What are the main side effects of the vinca alkaloids?
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VinBLASTine -> BLASTS your bone marrow (dose-related myelosuppression)
VinCRISTine -> angers the nerves in your hands and feet, much like crucifiction would (peripheral neuropathy) |
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What is the most important use of taxol?
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Metastatic breast and ovarian cancers
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What are the side effects of taxol? (4)
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Bone marrow suppression
Peripheral neuropathy Fibromyalgia Alopecia |
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How does tamoxifen work?
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anti-estrogen
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What drug is better than tamoxifen in chemoprevention in early stages of breat cancer?
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anastrazole
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How does anastrazole work?
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Inhibits aromatase -> blocks conversion of testosterone to estrogen
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Aside from chemoprevention, what is the other main use of anastrazole?
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Adjuvant treatment for metastatic breast cancer in post-menopausal women
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Which drug is an androgen antagonist?
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flutamide
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What cancer does flutamide treat?
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prostate cancer
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Which cancers does IL-2 treat? (3)
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Renal cell carcinoma
Melanoma Colorectal cancer |
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What is the main side effect of herceptin?
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Cardiotoxicity
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Which molecule on NSCLC is a target of newer mechanism-based anticancer agents?
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EGFR (a tyrosine kinase)
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What two newer mechanism-based anticancer agents can treat NSCLC?
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Iressa (small molecule)
Erlotinib (small molecule) |
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Which of the two EGFR antagonists has DEMONSTRATED efficacy against NSCLC?
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Iressa
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What population is iressa most effective in? Why?
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Asians -> due to higher rates of EGFR mutations
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What sort of drug is iressa?
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Small molecule inhibitor of EGFR
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What sort of drug is erlontinib?
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Small molecule inhibitor of EGFR
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Which drug is an angiogenesis inhibitor?
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Avastin
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What cancers are susceptible to avastin?
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Metastatic colon and rectal cancers
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What drug is a general tyrosine kinase antagonist?
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Gleevac (imatinib)
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What is the generic name for Gleevac?
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Imatinib
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Which tyrosine kinases are targeted by imatinib? (3)
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Bcr-Abl
c-kit PDGF-R |
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Which tumors are targeted by Gleevac? (3)
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CML (Bcr-abl)
GIST (c-kit) Glioblastoma (PDGF-R) |
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What are the main side effects of Gleevac? (3)
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Muscle cramps
Diarrhea RASH |
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Which cells have CD20?
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B cells
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What monoclonal antibody targets CD20?
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Rituximab
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What diseases are treated by anti-CD20?
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B cell lymphomas
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What diseases are treated by rituximab?
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B cell lymphomas
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Which cells have CD33?
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Cells of the myeloid/monocyte lineage
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What monoclonal antibody targets CD33?
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Gemtuzumab
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What diseases are treated by anti-CD33?
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CD33+ AML
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What diseases are treated by gemtuzumab?
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CD33+ AML
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What is the monoclonal antibody against EGF-R?
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Cetuximab
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What are anti-EGF-R antibodies used to treat?
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Colorectal cancers (not NSCLC, that’s iressa and erlotinib)
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