Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most
abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin.
The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic
client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed
attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous
oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors
that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired
immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the
process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging
results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being
under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel
drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification
of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and
emerging classical inhibitors.