Targeting Cell Survival Factors, HSF1 and HSPs, with a Specific Inhibitor for Cancer Therapy

Abstract

It has been known that major heat shock proteins, such as Hsp90 and Hsp70, and their transcription factor HSF1 are overexpressed in a wide range of cancer cells. Its biological significance, however, remains unclear. Recently, it has been recognized that HSF1 and HSPs are cell survival factors and essential for cancer cell development and progression, and the HSF1-HSPs system seems to be co-opted by cancer cells for their own survival under stressful conditions (low oxygen concentration, low nutrient, low pH). According to this conception, targeting HSF1 and HSPs with a specific inhibitor has been suggested for cancer therapy. Hsp90 inhibitors have long been studied from 1990ʼ not only in a basic research but also in clinical phase I, phase II, even phase III trials. Recently, several inhibitors of Hsp70 and HSF1 for the purpose of cancer therapy have been reported. In this review, basic researches aimed for cancer therapy targeting these survival factors (HSF1 and HSPs) with a specific inhibitor are summarized.