Term
| by chance discovery; used platinum electrode and observed no growth in bacteria, same observation in mammalian cells, realized Platin Chloride kills mammalian cells in vitro and can shrink tumors in rats and mice in vivo (development of drug) |
|
Definition
|
|
Term
| Targeted synthesis (development of drug) |
|
Definition
|
|
Term
| Screening of chemicals and natural productions (development of drug) |
|
Definition
| vinca alkaloids, Adriamycin, taxol |
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Term
|
Definition
| Mitoxantrone, carboplatin |
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Term
| analog of Adriamycin (Doxorubicin); used in patients who have HEART ISSUES because SE of Adriamycin is cardiotoxicity |
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Definition
|
|
Term
| analog of Cisplatin; used in patients with KIDNEY PROBLEMS because Cisplatin has nephrotoxicity |
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Definition
|
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Term
|
Definition
| Alkylating agents, antimetabolites, cytotoxic antibiotics, natural products |
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|
Term
| Cancer Chemotherapeutic Agents |
|
Definition
| Cytotoxic Agents, Hormones, Targeted Chemotherapeutic Agents |
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Term
| Cell cycle phase specific (need prolonged exposure or repeated doses) |
|
Definition
| antimetabolites, vinca alkaloids |
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Term
| Cell cycle phase non-specific (most effective against actively dividing cells but also effective in Go) |
|
Definition
| alkylating agents, cisplatin |
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Term
|
Definition
| refractory to chemotherapy |
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Term
|
Definition
|
|
Term
|
Definition
| Procarbazine, Antimetabolites, Hydroxyurea, Camptothecins |
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Term
|
Definition
| Bleomycin, Vinca alkaloids, taxanes |
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Term
|
Definition
|
|
Term
| Classic alkylating agents |
|
Definition
| Nitrogen mustards, Nitrosoureas |
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|
Term
| Non classic alkylating agents |
|
Definition
| Procarbazine, Bendamustine |
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Term
|
Definition
| mechlorethamine, Melphalan, Cyclophosphamide, Chlorambucil |
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Term
|
Definition
| carmustine (BCNU), lomustine (CCNU) |
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Term
|
Definition
| cisplatin, carboplatin, oxaliplatin |
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Term
|
Definition
| Classic, non-classic, and Platinum analogs |
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|
Term
| nitrogen mustard with smallest side chain; most active out of the alkylating agents |
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Definition
|
|
Term
| nitrogen mustard with a cyclic group and longer side chain causing it to only be a moderate anticancer drug |
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Definition
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|
Term
| Only alkylating agents that can cross the blood brain barrier; this is due to the side chain being lipophillic |
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Definition
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|
Term
| very common regimen for treatment of Hodgkin's disease sand non-Hogkin's lymphomas |
|
Definition
| Mechloroethamine, Vincristine (Oncovin), Procarbazine, Prednisone (MOPP)!! |
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Term
| Must be given IV by rapidly flowing infusion of saline; care must be taken to avoid extravasation--- any splash on hands causes blistering |
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Definition
|
|
Term
| Side effects of this drug include Myelosuppression, nausea/vomiting, alopecia, and menstrual irregularities |
|
Definition
| Mechloroethamine (a prototype of the nitrogen mustards) |
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Term
| Broad spectrum of activity; is a prodrug that is metabolized by CYP450 |
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Definition
|
|
Term
| Reactive species metabolite of Cyclophosphamide |
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Definition
|
|
Term
| Toxic metabolite of Cyclophosphamide |
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Definition
|
|
Term
| Side effects of this drug include Nausea/vomiting, bone marrow suppression, hemorrhagic cystitis** (ameliorated w/ SH donors and large fluid intake) |
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Definition
|
|
Term
| can pass blood brain barrier, useful in the treatment of CNS tumors |
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Definition
|
|
Term
| side effects include nausea/vomiting, delayed hematopoietic depression, CNS toxicity, pulmonary fibrosis with chronic use |
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Definition
|
|
Term
| N-methylated by liver microsomal enzymes, then function as an alkylating agent |
|
Definition
| non-classical alkylating agents |
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|
Term
| most active agent against malignant melanoma (silencing the gene-- inhibiting DNA and RNA synthesis) |
|
Definition
| non-classical alkylating agents (Temozolomide, Decacarbazine, Procarbazine) |
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|
Term
| Chloride dissociates --> reactive complex that reacts with water and DNA--> intrastrand cross link --> denaturation DNA |
|
Definition
| Platinum Analogs (Cisplatin, Carboplatin) |
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|
Term
| Nephrotoxic: should be administered with vigorous hydration + mannitol to avoid renal toxicity |
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Definition
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|
Term
| severe n/v ameliorated w/ 5-HT3 antagonists (decrease gastric motility); common treatment of testicular cancer |
|
Definition
|
|
Term
| Myelosuppression is the dose-limiting toxicity; these are phase specific and were developed by rational synthesis rather than empirical screening of anticancer drugs |
|
Definition
|
|
Term
| 3 major classes of antimetabolites |
|
Definition
| Folic acid analogs (Methotrexate); Pyrimidine analogs (5-Fluorouracil); Purine analogs and related inhibitors (6-MP) |
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|
Term
| competitively inhibits dihydrofolate reductase (inhibits 1 carbon transfer); leading to the blockade of the biosynthesis of thymidylate and purines required for DNA synthesis |
|
Definition
| Folic Acid Analogs (Methotrexate) |
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|
Term
| Is S-phase specific; can be administered intravenously, intra-arterially, intra-thecally, or orally; is eliminated mainly by the kidneys |
|
Definition
|
|
Term
| 2 differences between Folic Acid and Methotrexate |
|
Definition
N#10- FA = H
N#10 - MTX =CH3
Pteriding Ring FA = O
Pteriding Ring MTX= NH2 |
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|
Term
| inhibits Thymidylate synthetase by being converted to FDUMP so that DUMP cannot be converted to DTMP |
|
Definition
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|
Term
| used in the treatment of choriocarcinoma; in combo with other agents in the treatment of acute lymphoblastic leukemia and carcinoma of the breast, cervix, lung, head, and neck (maintenance with 6-MP) |
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Definition
|
|
Term
| Tumor can decrease active transport then it will not respond well to MTX. Give high doses of MTX and then you will get diffusion of MTX into the tumor. "rescue" normal cells with: |
|
Definition
|
|
Term
| Is MYELOSUPPRESSIVE producing severe leukopenia, bone marrow aplasia, and thrombocytopenia; Oral dose causes GI toxicity; prolonged low doses cause hepatic dysfunction; precipitation of 7-OH metabolites causes renal toxicity |
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Definition
|
|
Term
| Tumor cell resistance: tumor cells generate an increased concentration of this through gene amplification causing a major mechanism of tumor resistance to methotrexate |
|
Definition
|
|
Term
| Pyrimidine Analogs that are pro-drugs |
|
Definition
| 5-Fluorouracil, Cytarabine |
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|
Term
|
Definition
| 5-FU, Cytarabine, Gemcitabine |
|
|
Term
| Inside tumor cells it is activated to a "fraudulent" nucleotide, fdUMP |
|
Definition
|
|
Term
| is a phase NON-specific (unlike other antimetabolites!!) due to its RNA action |
|
Definition
|
|
Term
| exclusively used to treat solid tumors, especially breast, colorectal, and gastric tumors and squamous cell tumors of the head and neck; can cause myelosuppression, NV, and oral/GI ulceration |
|
Definition
|
|
Term
| Tumor Cell Resistance: 5-FU - due to increased synthesis of: |
|
Definition
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|
Term
| Analog of cytidine in which the ribose moiety has been replaced with an arabinose |
|
Definition
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|
Term
| Phosphorylated in vivo --> cytosine arabinoside triphosphate (ara CTP) which competitively inhibits DNA polymerase --> blocks DNA synthesis and causes cell death |
|
Definition
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|
Term
| Ara-CTP competes with dCTP and inhibits DNA polymerase, incorporates into DNA produces strand breaks and triggers apoptosis |
|
Definition
| Cytarabine (cytosine arabinoside, ara-C) |
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|
Term
| has a narrow clinical spectrum and is primarily used in combo with Daunorubicin or Thioguanine (6-TG) for the treatment of acute non-lymphocytic leukemia such as AML |
|
Definition
|
|
Term
| high doses can damage the liver, heart, and other organs |
|
Definition
|
|
Term
| Tumor cell resistance: depressed levels of kinase required for activation- leads to lack of phosphorylation and decreased inhibition of DNA synthesis; enhanced levels of deaminase that inactiveates the drug |
|
Definition
|
|
Term
|
Definition
| 6-mercaptopurine, 6-thioguanine, Fludarabine |
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|
Term
| are all pro-drug; must be converted to nucleotides, the active species; activation MUST occur in target cells |
|
Definition
| purines and purine analogs |
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|
Term
| all are rapidly broken down to inactive products, mainly in extra-tumor tissues. However nucleotides have longer half life; All interfere with several biochemical targets but inhibition of DNA synthesis appears important for all |
|
Definition
| Purines and purine analogs |
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|
Term
| only difference is -SH instead of -OH; "false" nucleotides-- inhibit synthesis |
|
Definition
|
|
Term
| structural analog of hypoxanthine (natural purine) |
|
Definition
|
|
Term
| must be converted intracellularly to the nucleotide 6-mercaptopurine ribose phosphate by hypoxanthine-guanine phosphoribosyl transferase (HGPRT); can also be converted to 6-mercaptopurine ribonucleotide |
|
Definition
|
|
Term
| converts 6-MP to an INVACTIVE form |
|
Definition
|
|
Term
| if on this drug you want to reduce the dose of 6-MP by 1/4; 6-MP commonly leads to hyper-uricemia (gout) |
|
Definition
|
|
Term
| cytotoxic because they inhibit de novo purine biosynthesis |
|
Definition
| 6-MP ribose phosphate and the methylated nucleoside |
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|
Term
| used primarily for the maintenance of remission in patients with acute lymphocytic leukemia and is given in combo with MTX for this purpose |
|
Definition
|
|
Term
| acute lymphocytic leukemia (ALL) treatment |
|
Definition
|
|
Term
| Tumor cell resistance (2 ways): Decreased drug activation by HGRPT (converts it to active form inside the cell); an increased inactivation by alkaline phosphase (degrades the drug) |
|
Definition
|
|
Term
| structural analog of guanine in which a sulfhydryl replaces a hydroxyl group |
|
Definition
|
|
Term
| cytotoxicity is due to feedback inhibition of purine biosynthesis by 6-TG ribose phosphate |
|
Definition
|
|
Term
| Used in the treatment of AML |
|
Definition
|
|
Term
| when given with allopurinol you do NOT need to reduce the dose |
|
Definition
|
|
Term
| is dephosphorylated to 2-fluoro-arabinofluranosyladenosine then phosphorylated intracellularly to triphosphate |
|
Definition
|
|
Term
| The triphosphate metabolite interferes with DNA synthesis and DNA repair through inhibition of DNA polymerases alpha and beta |
|
Definition
|
|
Term
| used in the treatment of non-Hodgkin's lymphoma and chronic leukemia (CLL) |
|
Definition
|
|
Term
| main dose-limiting toxicity: myelosuppression and immunosuppression. Patients are at risk for opportunistic infections |
|
Definition
|
|
Term
| major classes of natural products |
|
Definition
| antitumor antibiotics (anthracyclines, mitomycin, bleomycin); vinca alkaloids, taxanes and related drugs; camptothecins; epipodophyllotoxins |
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|
Term
| prototype; isolated from Sreptomyces peucetius in 1958; it contains an amino sugar and an antrhacycline ring |
|
Definition
|
|
Term
| structurally similar to doxorubicin, lacking the hydroxyl ring |
|
Definition
| Daunorubicin (Daunomycin) |
|
|
Term
| synthesized to reduce cardiotoxic effects; a synthetic anthracene |
|
Definition
|
|
Term
| 3 different MOAs: 1- intercalate into the base pairs in DNA minor groove 2- inhibit Top II enzyme preventing the relaxation and supercoiled DNA, thus blocking DNA transcription and replication, causing ds breaks 3- free radical damage of cell membrane |
|
Definition
|
|
Term
| does not have to penetrate cell-- generates superoxide quinine ring-- lipid peroxidation ** |
|
Definition
|
|
Term
| extensively bound to plasma proteins and tissues after IV administration! mainly metabolized by the liver; MUST BE ADMINISTERED IV! |
|
Definition
|
|
Term
| can cause severe tissue necrosis, can't be administered IM or SC; care must be taken to avoid extravasation during IV infusions or injections |
|
Definition
|
|
Term
| produces lower frequency of severe local reactions after inadvertent extravasation compared to doxorubicin and daunorubicin |
|
Definition
|
|
Term
| one of the most effective agents against SOLID TUMORS- also effective against acute leukemia and malignant leukemia |
|
Definition
|
|
Term
| most effective against lymphocytic and granulocytic leukemia! has little activity against solid tumors |
|
Definition
|
|
Term
| as effective as daunorubicin with less toxicity; also effective in some patients with advanced breast cancer |
|
Definition
|
|
Term
| Tumor cell resistance: due to reduced intracellular accumulation of the drug due to increased EFFLUX: amplification of the mdr1 gene/P170gp, known as MDR phenotype |
|
Definition
|
|
Term
| will block the multi-drug resistance pump (P-gp) and coule be used together with anti-tumor drugs |
|
Definition
|
|
Term
| can cause both acute and chronic cardiomyopathy; damage to cardiac cell mitochondria is IRREVERSIBLE |
|
Definition
| Doxorubicin, Daunorubicin and to a less extent Mitoxantrone |
|
|
Term
| Binds Fe and inhibit OH production; decreases lipid peroxidation (can administer with Anthracyclines to reduce heart issues) |
|
Definition
| Dexrazoxane (metal-chelating agent) |
|
|
Term
| antibiotic isolated from Streptomyces caespitosus; reduced and reacts with amino groups on guanine residues on adjacent base pairs in complementary DNA strands that result in cross linking inhibiting DNA synthesis |
|
Definition
|
|
Term
| cell cycle non-specific but maximum kill in G1 and S phases; effective against recurrent breast and colon cancer, metastatic or recurrent osteogenic and soft tissue sarcomas and bladder cancer |
|
Definition
|
|
Term
| Tumor cell resistance: reduced intracellular drug accumulation (like P170 MDR gp); activation or enhancement of DNA repair mechanisms; increased glutathione transferase (GST) activity |
|
Definition
|
|
Term
| clinical usefulness is limited due to SEs: bone marrow suppression, mucocutaneous toxicity, pulmonary toxicity, hemolytic-uremic syndrome; extravasation |
|
Definition
|
|
Term
| treatment for hemolytic-uremic syndrome (can occur with Mitomycin C) |
|
Definition
| prednisone, captopril, and heparin |
|
|
Term
| group of glycopeptides extracted from bacterium Streptomycces verticillus. Each individual molecule has a planer and an amine end |
|
Definition
|
|
Term
| The planer end of the molecule intercalates with DNA (Between GT and GC!) sequences, the other end binds to Fe++ and facilitates its oxidation to Fe+++ ---> generating oxygen free radicals that cleave DNA |
|
Definition
|
|
Term
| Cells in Go and G2 are most sensitive; one of the few drugs that acts on Go!! is inactivated in most tissues except skin and lungs by an enzyme; toxicity in skin and lungs occurs because they lack that enzyme |
|
Definition
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|
Term
| used in combo therapy only! |
|
Definition
|
|
Term
| BEP regimen (testicular cancer) |
|
Definition
| Bleomycin, Etoposide, Cisplatin |
|
|
Term
| ABVD regiment (Hodgkin's Lymphomas) |
|
Definition
| Doxorubicin, Bleomycin, Vinblastine, Decacarbazine |
|
|
Term
| Tumor cell resistance: high levels of bleomycin hydrolase activity; tumor cell mutation altering the sequence that is sensitive to bleomycin intercalation |
|
Definition
|
|
Term
| age related side effects, cumulative dose-related PULMONARY TOXICITY |
|
Definition
|
|
Term
| Tumor cell resistance: high levels of bleomycin hydrolase activity; tumor cell mutation altering the sequence that is sensitive to bleomycin intercalation |
|
Definition
|
|
Term
| age related side effects, cumulative dose-related PULMONARY TOXICITY |
|
Definition
|
|
Term
| M phase specific drugs; bind to tubulin dimers in cytoplasm --> inhibit assembly (polymerization) of microtubules --> arrest at metaphase (M phase) |
|
Definition
| Vinca Alkaloids (Vinblastine, Vincristine) |
|
|
Term
| Used in combo with Doxorubicin, Bleomycin, and Decacarbazine for Hodgkin's Lymphomas |
|
Definition
|
|
Term
| used with Cyclophosphamide, hydroxydauoribicin, and prednisolone for non-hodgekin's lymphomas |
|
Definition
|
|
Term
| used with Mechlorethamine, Proccarbazine, and Prednisolone for Hodgkin's lymphomas |
|
Definition
|
|
Term
| ABVD regimen for Hodgkin's Lymphomas |
|
Definition
| Doxorubicin, Bleomycin, Vinblastine, Decacarbazine |
|
|
Term
| CHOP regimen for non-Hodgkin's Lymphomas |
|
Definition
| Cyclophosphamide, Hydroxydauoribicin, Oncovin, Prednisolone |
|
|
Term
| MOPP regimen for non-Hodgkin's lymphomas |
|
Definition
| Mechlorethamine, oncovin, Procarbazine, Prednisolone |
|
|
Term
| Used in non-hodgekin's lymphomas, Hodgkin's lymphomas, treatment of solid tumors in children, tumors of the breast, cervix in adults. IN combo with prednisolone for the induction of remission of childhood leukemia |
|
Definition
|
|
Term
| Dose limiting neurotoxicity. Vesicant. Dose-dependent sensory impairment and then motor impairment at higher doses |
|
Definition
|
|
Term
| Myelosuppression (leukopenia within 4-10 days after treatment) |
|
Definition
|
|
Term
| Phlebitis or cellulitis, if the drugs extravasate during the injection, as well as n/v, diarrhea, alopecia |
|
Definition
| Vincristine and Vinblastine |
|
|
Term
| disrupt the equilibrium between free tubulin and microtubules by shifting it in the direction of ASSEMBLY, inhibiting depolarization--- cause both stabilization of microtubules and the formation of abnormal bundles of microtubules |
|
Definition
|
|
Term
| used in solid tumors: NSCLC< ovarian and breast cancers; 90% hypersensitivity rxns (premedicate with antihistamines and steroids, neuropathy, alopecia, necrosis w/ extravasation, |
|
Definition
|
|
Term
| and albumin-bound paclitaxel formulation-- can use instead and do not need to premedicate for hypersensitivity reactions |
|
Definition
|
|
Term
| is not used clinically becauseos f toxicity; isolated from a Chinese tree |
|
Definition
|
|
Term
| has a lactone ring susceptible to hydrolysis-- (hydroxyl deriviative of the compound cannot be taken up by the tumor cell, this derivative will cause severe myelosuppression, diarrhea, sever vomiting) |
|
Definition
|
|
Term
| more water soluble, can be taken up by active transport system into tumor cell, less toxicity (closed ring) |
|
Definition
|
|
Term
| The A ring shields the D lactone ring; less susceptible to hydrolysis and can be taken up by the tumor cell although it is actively metabolized to another active molecule |
|
Definition
|
|
Term
| both bind to Topoisomerase I! |
|
Definition
|
|
Term
|
Definition
|
|
Term
| binds to DNA/top I --> cleavable complex. this prevents DNA re-ligation, causing DNA damage during the S-phase (collision of replication fork) |
|
Definition
|
|
Term
| prodrug converted in the liver by the carboxyestrase enzyme to the SN-38 metabolite which is 1000 FOLD MORE POTENT! |
|
Definition
|
|
Term
| CPT-11 is a prodrug that is converted in the livery by a carboxyestrase enzyme into: |
|
Definition
|
|
Term
| after forming SN-38 metabolite, 2nd phase is conjugation of metabolite to be eliminated. If there is no conjugation then: |
|
Definition
| build up SN-38--- myelosuppression, etc. Mutation in enzyme is what causes you to not fulfill 2nd phase of metabolism |
|
|
Term
| second line therapy for ovarian and small lung cancers (1st line for ovarian is Cisplatin!) |
|
Definition
|
|
Term
| First line therapy for metastatic colon cancer in combo with 5-FU and Leucovorin |
|
Definition
|
|
Term
| For metastatic pancreatic cancer: |
|
Definition
| combo of 5-FU, leucovorin and oxaliplatin, Irinotecan |
|
|
Term
| increased risk for sever/life threatening neutropenia (sometimes need to do genotyping when taking Camptothecins) |
|
Definition
|
|
Term
| camptothecins cause diarrhea (25%): early during infusion treat with ____; late (>24 hours) use____ |
|
Definition
|
|
Term
| semisynthetic derivative of podophyllotoxins was isolated from American mayapple roote |
|
Definition
|
|
Term
| forms a ternary complex with DNA and top II leading to the formation of a cleavable complex, which causes DNA damage and cell death; can be oral of IV |
|
Definition
| Epipodophyllotoxins (Etoposide or VP-16) |
|
|
Term
| used in small cell lung cancer, germ cell tumors, and in combo with bleomycin for testicular cancer |
|
Definition
|
|
Term
| used for NHL, some leukemia; kills by ADCC and fixing complement (targets CD20 on B cells) |
|
Definition
|
|
Term
| targets HER2 on some breast cancers and gastric cancer |
|
Definition
|
|
Term
| antibody-drug conjugate; binds CD30 and is conjugated to a cytotoxic drug auristatin |
|
Definition
| Bretuximab vedotin (Adcetris) |
|
|
Term
| Recombinant IL-2 (cytokine) conjugated to diphtheria toxin; binds CD25 and the diphtheria toxin kills the target cell; used for leukemia nad lymphomas |
|
Definition
| Denileukin diftitox (ontak) |
|
|
Term
| mAb against CTLA4; used for malignant melanoma by blocking CTLA4 and promoting T cell activation |
|
Definition
|
|
Term
| autologous cellular immunotherapy cancer vaccine; used for prostate cancer |
|
Definition
|
|
Term
| cytokine that has severe side effects |
|
Definition
|
|
Term
| cytokine that seems to promote activation of T cells and act on tumor cells to slow proliferation; used for variety of different cancers |
|
Definition
|
|
Term
| used for chronic myelogenous leukemia (CML) and other leukemias that are Bcl-ABL+ |
|
Definition
|
|
Term
| binds/blocks intracellular site on epidermal growth factor receptor; blocks proliferation, inhibits angiogenesis |
|
Definition
|
|
Term
| bind and blocks growth factor itself, keeping ligand from being able to bind to the receptor and keep it from stimulating that pathway |
|
Definition
|
|
Term
|
Definition
|
|
Term
| used for multiple melanoma; constipate plasma cell and myeloma cell, block activation of NFKB, proteasome inhibitor |
|
Definition
|
|
Term
| used for multiple melanoma; constipate plasma cell and myeloma cell, block activation of NFKB, proteasome inhibitor |
|
Definition
|
|
