Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul 02707, Korea.
Cells. 2021 Mar 17;10(3):670. doi: 10.3390/cells10030670.
Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER)-resident member of the heat shock protein 90 (HSP90) family. In physiological conditions, it plays a vital role in regulating biological functions, including chaperoning cellular proteins in the ER lumen, maintaining calcium homeostasis, and modulating immune system function. Recently, several reports have shown the functional role and clinical relevance of GRP94 overexpression in the progression and metastasis of several cancers. Therefore, the current review highlights GRP94's physiological and pathophysiological roles in normal and cancer cells. Additionally, the unmet medical needs of small chemical inhibitors and the current development status of monoclonal antibodies specifically targeting GRP94 will be discussed to emphasize the importance of cell surface GRP94 as an emerging therapeutic target in monoclonal antibody therapy for cancer.
葡萄糖调节蛋白 94（GRP94）是内质网（ER）驻留的热休克蛋白 90（HSP90）家族成员。在生理条件下，它在调节生物功能方面发挥着至关重要的作用，包括在内质网腔中伴侣细胞蛋白、维持钙稳态和调节免疫系统功能。最近，有几项报告表明，GRP94 过表达在几种癌症的进展和转移中的功能作用和临床相关性。因此，本综述强调了 GRP94 在正常和癌细胞中的生理和病理生理作用。此外，还讨论了小分子抑制剂的未满足的医疗需求和专门针对 GRP94 的单克隆抗体的当前开发状况，以强调细胞表面 GRP94 作为癌症单克隆抗体治疗中新兴治疗靶点的重要性。
