Chemotherapy

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telomerases role in cancer

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the enzyme that provides immortality to the tumor cell

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restores the telomere in tumor cells, allowing indefinite growth

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telomerase

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complete remission means

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there are no signs or symptoms of the cancer

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partial remission is when

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there is a noticeable decrease of the cancer cells, few signs and symptoms are present

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seeks rapid reduction in tumor cell burden

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induction therapy

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seeks to complete or extend initial remission

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consolidation therapy

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seeks to sustain the remission for as long as possible

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maintenance therapy

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requires metabolic activation in absence of oxygen and is used to treat solid tumors where the oxygen supply is low

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Mitomycin C, an alkylating agent

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watch and wait is used mainly for

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slow growing cancers like prostate cancer and lymphomas

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chemotherapy drugs are toxic to tissues with a high growth fraction such as

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the bone marrow, skin, hair, GI tract, sperm

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Phase I trials test for

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toxicity

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Phase II tests for

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if the drug works

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Phase III tests for

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if the drug works better than what is currently available

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methotrexate and 5-fluorouracil are examples of what class of drugs

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antimetabolites

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give 3 examples of antimetabolites

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methotrexate, 5-fluorouracil, Ara-C (Cytarabine)

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structural analog of folate

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methotrexate

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common toxicities of antimetabolites

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bone marrow and GI toxicity

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would the multidrug resistance pump be more likely to act on an antimetabolite or a topoisomerase inhibitor?

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a topoisomerase inhibitor

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tight binding inhibitor of dihydrofolate reductase

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methotrexate

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the basis for selectivity of this drug involves the formation of polyglutamate derivates

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methotrexate

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analog of uracil

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5-flurouracil
antimetabolite

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typically used as the treatment for stage III colon cancer

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leucovorin + fluorouracil

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analog of deoxycytidine

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Cytosine Arabinoside (Ara-C)

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the most potent anti-leukemic drug

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cytosine arabinoside (Ara-C)

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analog of urea

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hydroxyurea

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inhibits ribonucleotide reductase which then inhibits DNA synthesis

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hydroxyurea

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commonly used for head and neck tumors as well as choriocarcinoma

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methotrexate

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used for acute and chronic leukemias as well as myeloproliferative disorders

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hydroxyurea

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6MP is often clinically used for

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maintenance therapy

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6TG is clinically used for

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remission induction in AML

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this entire class of drugs is S-phase specific

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antimetabolites

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anti-CD20 antibody drug

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rituximab

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unique toxicity of doxorubicin and daunomycin

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cardiotoxicity

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anthracycline antibiotics Adriamycin and Daunorubicin are from what class of chemo drugs

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Topoisomerase II inhibitors

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used to treat choriocarcinomas and neuroblastomas and is affected by the multi-drug resistant pump

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Actinomycin

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The source of this drug is the bark of the yew tree and its mechanism of action is that it prevents microtubule disassembly or depolymerization

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Taxol

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these drugs are derived from complex plant derivatives and cause microtubule disassembly

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Vincristine and Vinblastine

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list 3 drugs that interfere with microtubule function

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Vincristine, Vinblastine, and Taxol

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A unique toxicity of Vincristine is

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neurotoxicity

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Nitrogen mustards, sulfur mustards, nitroureas, and cyclophosphamide are all

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alkylating agents

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these drugs are chemically synthesized and may be monofunctional or bifunctional

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alkylating agents

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this class of drugs is primarily limited by its teratogenic and carcinogenic toxicities

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alkylating agents

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alkylates DNA, forms single strand breaks in DNA, and is used to treat islet carcinomas of the pancreas

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Streptozocin

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Streptozotocin is an alkylating agent that has a unique toxicity of

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nephrotoxicity

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these agents in general are associated with infertility and secondary malignancies

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alkylating agents

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this drug breaks DNA by a free radical mechanism and can cause pulmonary fibrosis

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Bleomycin

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these drugs have unique nephro and ototoxicities

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platinumcompounds

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activated in contact with water, binds DNA forming interstrand & intrastrand links

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platinumcompounds

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used for childhood acute leukemias, can cause hypersensitivity reactions

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asparaginase

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Tamoxifen is used for

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estrogen-positive breast tumors

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an antiestrogen used for breast cancer

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Tamoxifen

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an antiandrogen used for prostate cancer

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flutamide

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tamoxifen is associated with what type of cancer

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endometrial cancer

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these drugs are good for post menopausal women, they block local synthesis of estrogen in the breast, and are useful as maintenance therapy

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aromatase inhibitors

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a non-cytolytic agent that induces maturation of primitive promyelocytes

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ATRA - all trans retinoic acid

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arsenic trioxide is used as a second line therapy for

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APL

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a monoclonal antibody specific for the CD20 antigen located on the surface of B-cell lymphomas

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Rituximab

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an antibody specific for the HER2 protein located on metastatic breast carcinomas

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Trastuzumab- Herceptin

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the benefit of monoclonal antibody drugs

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highly specific targets, minimal toxicity

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protein kinase inhibitor used to induce apoptosis in CML

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Imatinib

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This is a topoisomerase I inhibitor that is not affected by the MDR pump, however its not clinically useful because it is too toxic

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Camptothecin