AdvancesinAnticancerDrugs创新.ppt

Advances in Anticancer Drugs Shu Yongqian 03-07-2005 “CANCER” Refers to a Malignant Neoplasm (New growth) Cancer cells can manifest: Uncontrolled proliferation. 无限增殖 Dedifferentiation. 去分化 Invasiveness. 浸润性 The ability to metastasize. 转移性 Leading causes of death  Epidemiology Heart Diseases Cancer Cerebrovascular Diseases Chronic Obstructive Lung Diseases Accidents Pneumonia Influenza Diabetes Mellitus Suicide Homicide HIV Infection Morbidity and Mortality of Main Cancers Phases of Oncogenesis Molecular Mechanism of Oncogenesis Neoplastic Cell Cycle Time Antineoplastic Agents and Biologic Response modifiers History 1865年，Lissauer 亚砷酸盐——白血病 1941年，耶鲁大学Goodman Gilman 氮芥——淋巴瘤 1941年，Huggins 雌激素——前列腺癌 1943年，Rhoads 烷化剂——恶性淋巴瘤 1948年，Farber 氨甲碟呤——小儿急性淋巴细胞性白血病 1961年，李明秋 联合化疗治疗睾丸肿瘤 1966年，Skipper 用L1210模型确立化疗药动学 1966年，Bruce 抗癌药物药理学研究 1966年，DjeRassi 大剂量化疗 1968年，Karnofsky 提出肿瘤内科学 1985年，Rosenberg 倡导过继性免疫疗法 1991年，首例肿瘤（黑色素瘤）基因治疗 ALKYLATING AGENTS烷化剂 NITROGEN MUSTARDS first developed in 1940s CCNS killing ability USES: Hodgkin’s disease lymphomas, leukemias, lung, breast, ovary, testes, brain, bladder Most widely used agent, often in combination with other agents. Types of alkylating agents Nitrogen mustards Ethylenimine derivatives Alkyl sulfonates Triazines Nitrosoureas Metal salts ANTIMETABOLITES抗代谢类 ACTIONS: -Antagonism of folate -purines, and pyrimidines needed for synthesis of nucleic acids -stops cell replication USES: -Solid tumors (breast, lung, liver, brain, colon,stomach) -Lymphomas, leukemias -S