BIIB021, an Hsp90 inhibitor: A promising therapeutic strategy for blood malignancies (Review).

BIIB021, an Hsp90 inhibitor: A promising therapeutic strategy for blood malignancies (Review). Oncol Rep. 2018 May 08;: Authors: He W, Hu H Abstract Heat shock proteins (HSPs) are molecular chaperones that are consistently increased to help cells survive under conditions of stress. As a member of the Hsps, Hsp90 is involved in protein post‑translational maturation and disposition. This protein is ubiquitously expressed in normal cells. However, in cancer cells and particularly in hematological malignancies, Hsp90 is unexpectedly abundant to maintain levels of proteins vital for cancer pathology. Hsp90 inhibitors can target the ATP domain of Hsp90 and prohibit its exchange of ADP for ATP, leading to the degradation of client proteins and disruption of signaling cascades. Concomitantly, Hsp90 inhibitors induce tumor cell apoptosis, promote cell cycle arrest and abrogate microenvironment‑derived cytoprotection. Geldanamycin, a benzoquinone antineoplastic antibiotic isolated from the bacterium Streptomyces hygroscopicus, and its derivative, 17‑AAG, were first developed as Hsp90 inhibitors and exhibited effective anticancer potency. Whereas, severe side effects and low solubility restricted their application at the clinical level, BIIB021, a novel and fully synthetic inhibitor of Hsp90, is water soluble and well‑tolerated. Beyond degrading oncogenic protein, BIIB021 can overcome multidrug resistance and potentiate the effects of ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research