Muhammad Lateef A, Saad Fred
a 1 Institut du cancer de Montréal, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Quebec, Canada.
Expert Rev Anticancer Ther. 2015;15(9):1049-61. doi: 10.1586/14737140.2015.1064769.
Resistance to cancer treatment can arise through multiple mechanisms and negatively impacts on progression rates and survival times. New therapies targeting pathways underlying resistance would improve treatment outcomes and be of particular value in the treatment of prostate cancer, many of whom develop tumors refractory to radiation, hormonal therapy and chemotherapy regimens. The improved understanding of metastatic castration resistant prostate cancer progression mechanisms has broadened the therapeutic window by unveiling multiple molecular targets. Several approaches are being investigated to overcome resistance in prostate cancer, including the use of novel taxanes and tubulin inhibitors, and the inhibition of cell survival pathways. This review focuses on clusterin, a small heat-shock-like protein that is overexpressed in many types of solid tumors; we summarize the preclinical and clinical evidence supporting the rationale for targeting clusterin as a means to resensitize prostate tumors to radiation and chemotherapy agents.
癌症治疗耐药可通过多种机制产生，并对疾病进展速度和生存时间产生负面影响。针对耐药潜在通路的新疗法将改善治疗效果，对前列腺癌的治疗具有特殊价值，因为许多前列腺癌患者会出现对放疗、激素治疗和化疗方案难治的肿瘤。对转移性去势抵抗性前列腺癌进展机制的深入了解，通过揭示多个分子靶点拓宽了治疗窗口。目前正在研究多种方法来克服前列腺癌的耐药性，包括使用新型紫杉烷和微管蛋白抑制剂，以及抑制细胞存活通路。本综述聚焦于簇集素，一种在多种实体瘤中过表达的小热休克样蛋白；我们总结了临床前和临床证据，支持将簇集素作为使前列腺肿瘤对放疗和化疗药物重新敏感的一种手段的理论依据。
