HSP27: Inhibitors

Due to its anti-apoptotic effects and the cytoprotection against chemotherapeutic drugs, Hsp27 has been proposed as a therapeutic target for over 20 years and this is supported by the publication of more recent reviews^97,98. Thus, Hsp27 modulators can decrease the protective function of the protein in cell apoptotic regulation^99,100,101. These agents exhibit promising antitumor activities in preclinical models of a variety of tumors expressing high levels of Hsp27 and may have significant clinical potential^102,103. So far, the most effective strategy to target Hsp27 is antisense oligonucleotides (ASO) or siRNA,⁹⁰ which can decrease Hsp27 expression in in vitro cell culture and in vivo xenograft as well^101,104. The fourth generation ASO of Hsp27, OGX-427¹⁰², has shown clinical evidence of antitumor activity despite the limitations associated with ASO administration. The results emphasizes that Hsp27 is a good oncotherapeutic target. Small molecule Hsp27 modulators without the administration problems are highly possible to show even better clinical outcome.