课件：《肿瘤内分泌治疗》PPT课件.pptVIP

雌激素刺激乳腺癌细胞的生长，因此乳腺癌为激素依赖型肿瘤，抑制或消除雌激素的作用成为内分泌治疗的主要任务。 内分泌疗法通过两个途径实现： 1 抑制雌激素的生物合成。如芳香化酶抑制剂，作用于雌激素生物合成的最后一步。再如LH-RH类似物、孕激素，抑制促性腺激素的合成，减少雌激素的生成。 2 阻断雌激素与其肿瘤细胞受体结合——雌激素受体拮抗剂 ，如他莫昔芬。 因此，老年肺癌面临着以下的几个困境： 往往被排除在临床试验之外； 往往接受未经验证或不够充分的治疗； 往往仅基于回顾性分析而建立治疗标准； 老年肺癌的标准治疗不应仅仅基于回顾性分析。我们有必要纳入更多的老年受试者、开展针对老年肿瘤的试验，以制定出更理想的治疗方案。 Reference Gridelli C, Langer C, Maione C, et al, J Clin Oncol 2007; 25: 1898-1907. The above slide presents a generalised view covering both pre- and postmenopausal situations LHRH 黄体生成素释放激素 There are 2 types of antiaromatase agents, which differ structurally and in their mechanism of action. Kuerer et al 2001/142/T1 The steroidal inactivator exemestane is structurally similar to androstenedione, the natural substrate of aromatase. Exemestane irreversibly inactivates aromatase, resulting in lower levels of estrogen. Aromasin PI/1/4 Formestane, available in the Europe, is also a steroidal inactivator.Kuerer/2001/142/T1 Letrozole and anastrozole are nonsteroidal agents that reversibly inhibit aromatase. Kuerer et al 2001/140/2/6-141/3/1,142/T1 Kuerer HM, Buzdar AU, Singletary SE. Biologic basis and evolving role of aromatase inhibitors in the management of invasive carcinoma of the breast. J Surg Oncol. 2001;77:139-147. Aromasin (exemestane) [package insert]. Kalamazoo, MI: Pharmacia Corporation; 1999. Nonsteroidal inhibitors reversibly bind to the heme part of the aromatase enzyme complex. They bind noncovalently, and decrease estrogen production. Androgen molecules may displace inhibitors, thus restoring aromatase activity. Brueggemeier 1994/32/2/3, 34/1/1 The interaction between the enzyme and the inhibitor stabilizes aromatase and prevents its degradation. Blocking of proteolytic degradation causes an increase in the amount of aromatase present after administration of a nonsteroidal inhibitor. Harada et al 1999/216/2/3, 217/1/3 Steroidal inactivators mimic the natural substrate androstenedione. They bind covalently (irreversibly) to the aromatase subs