Defective apoptosis underlies chemoresistance in ovarian cancer
Defective apoptosis underlies chemoresistance in ovarian cancer
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DOI：
10.1007/978-0-387-68969-2_16
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Liu, J. Rebecca
中科院分区：
文献类型：
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作者：
Hajra, Karen M.;Tan, Lijun;Liu, J. Rebecca
卵巢癌是女性生殖系统中第二常见也是最致命的恶性肿瘤。2006年，将诊断出20,000多例新的卵巢癌病例，其中大多数是晚期(III期或IV期)。生存率因年龄而异，新发卵巢癌患者的1年和5年生存率分别为76%和45%(1)。随着确诊时分期的增加，存活率急剧下降。卵巢癌总体预后较差的主要原因是诊断的晚期和化疗耐药性的产生，从而限制了对复发疾病的治疗。虽然最初对化疗的反应相当好，但大多数患者会复发，随着时间的推移，他们的肿瘤对当前的治疗方式变得耐药(23)。因此，识别和调节化疗耐药的机制是改善卵巢癌患者预后的关键。目前卵巢癌的标准辅助治疗是以铂类药物和紫杉醇为基础的联合化疗。癌症治疗的基本原则是选择性地杀死恶性肿瘤细胞，同时限制对正常细胞的毒性。多项研究表明，含铂药物，如顺铂和卡铂，通过触发被称为内在凋亡途径的程序性细胞死亡途径来杀死癌细胞(17，28)。研究已经发现，在耐药细胞中，执行这种细胞死亡级联反应的分子发生了变化(17，28)。我们将讨论在卵巢癌细胞中发现的特殊细胞缺陷，以及克服这些缺陷和恢复化疗敏感性的潜在治疗方法，特别强调卵巢癌中的凋亡体缺陷。
Ovarian cancer is the second most common and the most lethal of malignancies arising in the female reproductive system. In 2006, over 20,000 new cases of ovarian cancer will be diagnosed, with the majority of these being advanced disease (stage III or stage IV). Survival varies by age, with overall 1-year and 5-year survival rates for new ovarian cancer patients of 76% and 45%, respectively (1). Survival rates drop dramatically with increasing stage at the time of diagnosis. The overall poor prognosis of ovarian cancer is largely attributable to both the late stage of diagnosis and the development of chemoresistance that limits treatment for recurrent disease. Although initial responses to chemotherapy are quite good, the majority of patients develop recurrent disease, and over time their tumors become resistant to current treatment modalities (23). Thus, identification and modulation of the mechanisms that underlie chemoresistance is central to improving patient outcomes for ovarian cancer.The standard adjuvant therapy for ovarian cancer at this time is combination chemotherapy with a platinum-based drug and paclitaxel. The underlying principle of cancer therapy is the selective killing of malignant cells while limiting toxicity to normal cells. Multiple studies have demonstrated that platinum-containing agents, such as cisplatin and carboplatin, kill cancer cells by triggering a pathway of programmed cell death known as the intrinsic pathway of apoptosis (17, 28). Research has identified alterations in the molecules that carry out this cell death cascade in cells that are chemoresistant (17, 28). The specific cellular defects identified in ovarian cancer cells and potential therapeutic approaches to overcome these defects and restore chemosensitivity will be discussed, with specific emphasis on apoptosome defects in ovarian cancers.