抗恶性肿瘤药34幻灯片.pptVIP

Learning Objectives 1. Mastering the classification of antineoplastic agents according to both mechanisms of action and action on the phase of proliferation cycle. 2. Mastering the toxicity of antineoplastic drugs and general rules of combination therapies for cancer treatment. Part One Classification of Antineoplastic Agents Classification according to structure Alkalyting agent Antimetabolites Antitumor antibiotics Plant alkaloids Hormonal agents Platinum compounds Others Classification according to mechanism of action Drugs affecting biosynthesis of nucleic acid Drugs destroying DNA structure and function Drugs interfering with transcription and blocking RNA synthesis Drugs affecting protein synthesis Hormonal agents Classification according toeffect on cell proliferation kinetics Tumor cell phase G0 phase Cell cycle: G1→ S → G2 → M Anticancer drugs Cell cycle nonspecific agents (CCNSA) Cell cycle specific agent (CCSA) Part Two Antineoplastic Agents 2.1 Drugs affecting nucleic acid synthesis (antimetabolites) 2.1.1 Methothrexate (MTX) CCSA (S phase) Mechanism: inhibit dihydrofolate reductase (DHFR), interfering synthesis of tetrahydrofolic acid Clinical uses: childhood acute lymphoblastic leukemia and chorioepithelioma Toxicity: myelosuppression Rescue method: calcium leucovorin 2.2 Drugs affecting protein synthesis Vinblastine (VLB) Vincristine (VCR) Podophyllotoxins : teniposide（VM-26） and etoposide（VP-16） Taxanes: taxol taxotere Haffingtonine Homoharringtonine L-asparaginase 2.2.1 Vinblastine（VLB） vincristine（VCR ） - Mechanism of action bind specifically to the microtubular protein tubulin in dimeric form, terminate assembly of microtubules and result in mitotic arrest at metaphase, cause dissolution of the mitotic spindle and finally interfere with chromosome segregation 2.2.2 Taxol taxotere Mechanism Enhance tubulin polymerization and promote microtubule assembly Clinical uses: First choice for ovarian and advanced breast cancer Toxici