Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart Street, Kingston, ON, Canada K7L 3N6.
Biosci Rep. 2012 Aug;32(4):361-74. doi: 10.1042/BSR20110125.
Since cancer is one of the leading causes of death worldwide, there is an urgent need to find better treatments. Currently, the use of chemotherapeutics remains the predominant option for cancer therapy. However, one of the major obstacles for successful cancer therapy using these chemotherapeutics is that patients often do not respond or eventually develop resistance after initial treatment. Therefore identification of genes involved in chemotherapeutic response is critical for predicting tumour response and treating drug-resistant cancer patients. A group of genes commonly lost or inactivated are tumour suppressor genes, which can promote the initiation and progression of cancer through regulation of various biological processes such as cell proliferation, cell death and cell migration/invasion. Recently, mounting evidence suggests that these tumour suppressor genes also play a very important role in the response of cancers to a variety of chemotherapeutic drugs. In the present review, we will provide a comprehensive overview on how major tumour suppressor genes [Rb (retinoblastoma), p53 family, cyclin-dependent kinase inhibitors, BRCA1 (breast-cancer susceptibility gene 1), PTEN (phosphatase and tensin homologue deleted on chromosome 10), Hippo pathway, etc.] are involved in chemotherapeutic drug response and discuss their applications in predicting the clinical outcome of chemotherapy for cancer patients. We also propose that tumour suppressor genes are critical chemotherapeutic targets for the successful treatment of drug-resistant cancer patients in future applications.
由于癌症是全球主要死因之一，因此迫切需要找到更好的治疗方法。目前，化疗仍然是癌症治疗的主要选择。然而，这些化疗药物在癌症治疗中取得成功的主要障碍之一是，患者在初始治疗后往往没有反应或最终产生耐药性。因此，鉴定与化疗反应相关的基因对于预测肿瘤反应和治疗耐药性癌症患者至关重要。一组常见丢失或失活的基因是肿瘤抑制基因，它们可以通过调节细胞增殖、细胞死亡和细胞迁移/侵袭等各种生物学过程促进癌症的发生和发展。最近，越来越多的证据表明，这些肿瘤抑制基因在癌症对各种化疗药物的反应中也起着非常重要的作用。在本综述中，我们将全面概述主要的肿瘤抑制基因[Rb（视网膜母细胞瘤）、p53 家族、细胞周期蛋白依赖性激酶抑制剂、BRCA1（乳腺癌易感基因 1）、PTEN（第 10 号染色体缺失的磷酸酶和张力蛋白同源物）、Hippo 通路等]如何参与化疗药物反应，并讨论它们在预测癌症患者化疗临床结局中的应用。我们还提出，肿瘤抑制基因是未来治疗耐药性癌症患者成功化疗的关键治疗靶点。
