Anti-Cancer Flashcards
Methotrexate
*ant-metabolite
- Folic acid analog, inhibits DHF reductase = dec. dTMP = dec. DNA & protein synthesis.
- Uses:
- -Cancers: leukemias, lymphomas, choriocarcinoma, sarcomas.
- -Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD.
- Tox: BMS (reversible w/leucovorin), Macrovesicular fatty change in liver, Mucositis, Teratogenic.
5-fluorouracil (5-FU)
*ant-metabolite
- Complexes folic acid & inhibits thymidylate synthase = dec. dTMP = dec DNA and protein synthesis.
- flucytosine (anti-fungal) metabolized to 5-FU
- Use: Colon cancer, pancreatic cancer, basal cell carcinoma (topical).
- Tox: BMS (reversible w/uridine), photosensitivity.
**causes thymine-less death.
Cytarabine (arabinofuranosyl cytidine)
*ant-metabolite
- Pyrimidine analog => inhibition of DNA polymerase.
- Use: leukemias, lymphomas.
- Tox: BMS, megaloblastic anemia.
Azathioprine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG)
-Purine (thiol) analogs = dec. de novo purine synthesis. Activated by HGPRT. Inhibits PRPP amidotransferase (PRPP -> IMP)
-Use: Preventing organ rejection, RA, SLE (azathioprine).
Leukemia, IBD (6-MP, 6-TG).
-Tox: Bone marrow, GI, liver. Azathioprine & 6-MP are
metabolized by xanthine oxidase; thus both have inc.
toxicity with allopurinol, which inhibits their metabolism.
Dactinomycin (actinomycin D)
- Intercalates in DNA.
- Use: Wilms tumor, Ewing sarcoma, rhabdomyosarcoma. Used for childhood tumors (“children act out”).
- Tox: BMS
Doxorubicin (Adriamycin), daunorubicin
-Generate free radicals & intercalate in DNA = dec. DNA rep.
-Use: Solid tumors, leukemias, lymphomas.
-Tox: Cardiotoxicity (dilated cardiomyopathy), BMS, alopecia. Toxic to tissues following extravasation.
Dexrazoxane (iron chelating agent), used to prevent
cardiotoxicity.
Bleomycin
- Free radical formation
- Use: Testicular cancer, HL.
- Tox: Pulm. fibrosis, skin changes, mucositis.
- *NO BMS.
Cyclophosphamide, ifosfamide
*Alkylating agents
-Covalently X-link DNA at guanine N-7. Require
bioactivation by liver.
-Use: Solid tumors, leukemia, lymphomas, and some brain cancers.
-Tox: BMS; hemorrhagic cystiti (prevent w/mesna).
Nitrosoureas (carmustine, lomustine, semustine,
streptozocin)
*Alkylating agents
- Require bioactivation. Cross BBB. Cross-links DNA.
- Use: Brain tumors (including glioblastoma multiforme).
- Tox: CNS tox. (convulsions, dizziness, ataxia).
Busulfan
*Alkylating agent
- Cross-links DNA.
- Use: CML. Also used to ablate patient’s bone marrow before bone marrow transplantation.
- Tox: Severe BMS, pulm. fibrosis, hyperpigmentation.
Vincristine, vinblastine
-Inhibit MT polymerization.
-Use: Solid tumors, leukemias, and lymphomas.
-Tox:
–Vincristine = neurotoxicity (areflexia, peripheral neuritis),
paralytic ileus. **NO BMS
–Vinblastine = blasts bone marrow (suppression).
Paclitaxel, other taxols
- inhibit MT depol.
- Use: Ovarian and breast carcinomas.
- Tox: BMS, alopecia, hypersensitivity.
Colchicine
- Inhibit MT polymerization (impairing leukocyte chemotaxis and degranulation).
- Use: Gout, cancer.
- Tox: GI
Cisplatin, carboplatin
- Cross-link DNA
- Use: Testicular, bladder, ovary, and lung carcinomas.
- Tox: Nephrotoxicity and acoustic nerve damage. Prevent nephrotox w/amifostine and chloride diuresis.
- *NO BMS
Etoposide, teniposide
- inhibit topoisomerase 2 => inc. DNA degradation.
- Use: Solid tumors (particularly testicular and small cell lung cancer), leukemias, lymphomas.
- Tox: BMS, GI irritation, alopecia.
Irinotecan, topotecan
- inhibit topoisomerase 1 => prevent DNA unwinding & replication.
- Use: Colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan).
- Tox: Severe BMS, diarrhea.
Hydroxyurea
- Inhibits ribonucleotide reductase => dec. DNA Synthesis (S-phase specific). Also inc. Hb-F.
- Use: Melanoma, CML, sickle cell disease.
- Tox: Bone marrow suppression, GI upset.
Prednisone, prednisolone
-Trigger apoptosis. May even work on nondividing cells.
-Use: CLL, NHL.
-Tox: Cushing-like symptoms; weight gain, central obesity, muscle breakdown, cataracts, acne,
osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis.
Tamoxifen
-SERM
Breast = antagonist
Bone = agonist
Endometrum = agonist
raloxifene
-SERM
Breast = antagonist
Bone = agonist
Endometrum = antagonist
Trastuzumab (Herceptin)
- Kills Her2 (c-erbB2), a tyrosine kinase receptor) positive breast cancer cells.
- Tox: cardiotoxicity
- “Heart”ceptin.
Imatinib (Gleevec)
- Tyrosine kinase inhibitor of bcr-abl (Ph. chrom. fusion gene in CML) and c-Kit (common in GI stromal tumors).
- Tox: fluid retention
Rituximab
- Mab against CD20, found on most B-cell neoplasms.
- Use: NHL, rheumatoid arthritis (with MTX), ITP.
- Tox: inc. risk of progressive multifocal leukoencephalopathy.
Vemurafenib
- Inhibitor of forms of the B-Raf kinase with the V600E mutation.
- Use: metastatic melanoma
