Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology, Rourkela, 769008, Odisha, India.
Epigenetics and Cancer Research Laboratory, Department of Life Science, National Institute of Technology, Rourkela, 769008, Odisha, India.
Biochim Biophys Acta Rev Cancer. 2021 Apr;1875(2):188500. doi: 10.1016/j.bbcan.2020.188500. Epub 2020 Dec 29.
Clusterin (CLU) is an evolutionary conserved molecular chaperone present in different human tissues and fluids and established to be a significant cancer regulator. It controls several cancer-associated cellular events, including cancer cell proliferation, stemness, survival, metastasis, epithelial-mesenchymal transition, therapy resistance, and inhibition of programmed cell death to support cancer growth and recurrence. This multifunctional role of CLU makes it an ideal target for cancer control. More importantly, genetic and antisense-mediated (OGX-011) inhibition of CLU enhances the anticancer potential of different FDA-approved chemotherapeutic drugs at the clinical level, improving patient's survival. In this review, we have discussed the detailed mechanism of CLU-mediated modulation of different cancer-associated signaling pathways. We have also provided updated information on the current preclinical and clinical findings that drive trials in various cancer types for potential targeted cancer therapy.
簇集蛋白 (CLU) 是一种进化上保守的分子伴侣，存在于不同的人体组织和体液中，被确定为重要的癌症调控因子。它控制着几种与癌症相关的细胞事件，包括癌细胞增殖、干细胞特性、存活、转移、上皮-间充质转化、治疗抵抗以及程序性细胞死亡的抑制，以支持癌症的生长和复发。CLU 的这种多功能作用使其成为癌症控制的理想靶点。更重要的是，CLU 的遗传和反义抑制 (OGX-011) 在临床水平上增强了不同 FDA 批准的化疗药物的抗癌潜力，提高了患者的生存率。在这篇综述中，我们讨论了 CLU 介导的不同癌症相关信号通路调节的详细机制。我们还提供了关于当前临床前和临床发现的最新信息，这些发现推动了各种癌症类型的试验，以进行潜在的靶向癌症治疗。
