Title:Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease
Volume: 16
Issue: 25
Author(s): Liza Shrestha, Alexander Bolaender, Hardik J. Patel and Tony Taldone
Affiliation:
Keywords:
HSP90, Chaperone, Inhibitor, Cancer, N-Terminal.
Abstract: Heat shock proteins (HSPs) present as a double edged sword. While they play an important
role in maintaining protein homeostasis in a normal cell, cancer cells have evolved to co-opt HSP
function to promote their own survival. As a result, HSPs such as HSP90 have attracted a great deal of
interest as a potential anticancer target. These efforts have resulted in over 20 distinct compounds entering
clinical evaluation for the treatment of cancer. However, despite the potent anticancer activity
demonstrated in preclinical models, to date no HSP90 inhibitor has obtained regulatory approval. In
this review we discuss the unique challenges faced in targeting HSPs that have likely contributed to
their lack of progress in the clinic and suggest ways to overcome these so that the enormous potential
of these compounds to benefit patients can finally be realized. We also provide a guideline for the future development of
HSP-targeted agents based on the many lessons learned during the last two decades in developing HSP90 inhibitors.
