抗恶性肿瘤药03幻灯片.pptVIP

Worldwide overall annual cancer incidence Death rates for heart disease and cancer among people younger and older than age 85. 癌症特点 不受机体约束的增殖 与细胞增殖有关的基因被开启或激活； 与细胞分化有关的基因被关闭或抑制； 局部侵袭 (local invasiveness) 转移 (metastasis) 低分化 (less differentiated) 保留原组织一些特征 The Aim of Cancer Treatments Palliation——缓解症状，姑息治疗 Alleviation of symptoms Increased survival and improved quality of life Remission ——临床治愈 all macroscopic and microscopic features of the cancer disappear, though disease is known to persist Cure——治愈 all the cells of the clone must be destroyed 目前主要治疗手段 Six Established Therapeutic Modalities Surgery (外科手术)：实体瘤 Rediotherapy (放射治疗)：鼻咽癌、早期声带癌 Cytotoxic chemotherapy (化学治疗,化疗) Endocrine therapy (内分泌治疗) Immunotherapy (免疫治疗) Biological/targeted therapy (生物治疗) CTM treatment (中医治疗) Multi-modality treatment 肿瘤化疗的障碍 毒性反应 选择性差 “杀敌一千，自损五百” 耐药性 不敏感 抗恶性肿瘤药的三大趋势 从单一治疗向综合治疗 从单一药物到联合用药 从姑息治疗向根治治疗 从细胞毒性药物向针对机制多环节新型药物 Cell Cycle and Cancer 细胞周期的调控 Cell Cycle 生长比率 (Growth fraction, GF) GF大：早期。急性白血病、何杰金病、绒癌，对药物敏感； GF小：晚期。慢性白血病、多数实体瘤，对药物敏感↓ 静止细胞群 非增殖细胞群（G0期） 对药物不太敏感，是复发根源。 Gompertzian tumor growth The growth fraction of a tumor declines exponentially over time. The growth rate of a tumor peaks before it is clinically detectable. Tumor size increases slowly, goes through an exponential phase, and slows again as the tumor reaches the size at which limitation of nutrients or auto- or host regulatory influences can occur. The maximum growth rate occurs at 1/e, the point at which the tumor is about 37% of its maximum size. Tumor becomes detectable at a burden of about 109 (1 cm3) cells and kills the patient at a tumor cell burden of about 1012 (1 kg). Efforts to treat the tumor and reduce its size can result in an increase in the growth fraction and an increase in growth rate. Gompertzian tumor growth 抗肿瘤药的发展 1946年，化学战中的细胞毒——氮芥及其衍生物有抑瘤作用，但选择性差，故称细胞毒剂(cytotoxic agents)。 50年代中期之后的十余年，寻找毒性较低的抑制免疫功能的抗肿瘤药物，如抗嘌呤类(6-MP)、阿霉素等抗生素。 70年代中期，由抗细胞繁殖药物转向多因素的免疫调节药。 今近年，肿瘤的生物治疗受到重视。 The Goal of