2016-11-04
cytotoxic agents
Cell Cycle-nonspecific (CCNS) agents Alkylating agents Carmustine Chlorambucil, Melphalan, Cyclophosphamide, Thiotepa Anthracyclines Daunorubicin, Doxorubicin, Epirubicin Antitumor antibiotics Mitomycin Platinum analogs Carboplatin Cisplatin Oxaliplatin
Cell cycle nonspecific (CCNS) agents S (2-6h) G 2 (2-32h) M (0.5-2h) G 1 G 0
Cell cycle specific (CCS) agents
Cell cycle-specific (CCS) agents Antimetabolites (S Phase) 5-Fluorouracil (5-FU) Methotrexate (MTX) Topoisomerase II inhibitor (S-G2 phase) Etoposide Taxanes (M Phase) Docetaxel Paclitaxel Vinca alkaloids (M Phase) Vinblastine, Vincristine, Vinorelbine Antitumor antibiotics (G2-M Phase) Bleomycin
Antimetabolites S
(methotrexate, MTX) (DHFR) dtmp DNA
(fluorouracil, 5-FU) dump dtmp
mercaptopurine 6-MP
hydroxycarbamide, HU
cytarabine, Ara-C DNA
Antimetabolites 1 2 3 4 5 DNA
DNA DNA (topoisomerase) DNA DNA DNA DNA (topoisomerase)
DNA
+DNA- DNA DNA
Alkylating agents (nitrogen mustard) (Cyclophosphamide) (Thiotepa, Riethylene, Thiophosphoramide TSPA) (Busulfan, (Carmustine,,
DNA A Cisplatin Carboplatin Oxaliplatin
cisplatin,,ddp DNA
bleomycin, BLM DNA, G2
(topoisomerase) camptothecin, CPT DNA : S : DNA I
Etoposide, VP16 DNA II S G2
teniposide, VM-26,
D
doxorubicin, ADM RNA
M Vinblastin : Vincristine :
Paclitaxel M
Docetaxel
Harringtonine Homoharringtonine
L-ASP
1. 2.
Hormone Drugs For Prostate Cancer Class Antiandrogens Drugs (flutamide) Function & target Androgen (testosterone) antagonist & uptake inhibitor GnRH Agonists goserelin (leuprorelin) Decreased androgen or estrogen production Estrogens (diethylstilbestrol) Estrogen receptor agonist; antagonizes androgens
Hormone Drugs For Breast Cancer Class Drugs Function & target Cancer Androgens (methyltestosterone) testosterone propionate fluoxymesterone Aromatase inhibitor, testosterone receptor agonist Breast GnRH Agonists goserelin (leuprorelin) Decreased androgen or estrogen production Prostate & breast Antiestrogens (tomoxifen) toremifene Estrogen receptor antagonist; prevents tumor growth stimulation Breast Aromatase Inhibitors (Anastrozole) (letrozole) Reduces levels of circulating estradiol Advanced breast cancer (aminoglutathimide)
EGFR tyrosine kinase inhibitors Gefitinib Anti-EGFR mabs Trastuzumab ATP TK TK
Trastuzumab (Herceptin): Humanized Anti-HER2 Antibody HER2 epitopes recognized by hypervariable murine antibody fragment Human IgG-1 Targets HER2 protein High affinity (K d = 0.1 nm) and specificity 95% human, 5% murine Decreases potential for immunogenicity Increases potential for recruiting immune effector mechanisms Monoclonal antibody targeting of HER2 growth factor receptor is the first FDA-approved use of biologic therapy in breast cancer
Gefitinib Trastuzumab Her2+
VEGF Signal Inhibition bevacizumab Tumor VEGF Rh-Endostatin Angiogenesis
Imatinib (Gleevec ) Competitively inhibits tyrosine kinase activity of BCR-ABL BCR-ABL tyrosine kinase is present in virtually all patients with chronic myelogenous leukemia (CML) and some patients with acute lymphoblastic leukemia (ALL)
bortezomib 26S (potent, selective, and reversible 26S proteasome) multiple myeloma multiple myeloma
all-trans retinoid acid ATRA acute promyelocytic leukemia, APL active in patients with acute promyelocytic leukemia (APL) (RARα/PML) induce terminal differentiation
(As2O3) (As2O3) induce differentiation through degradation of the chimeric PML/RARa protein
1 (recruitment) : - : - 2 (synchronization) -
1. 2.
2
1. 2. 3.