Heat Shock Protein 27 (Hsp27, Hspb1) Is Up-Regulated By Targeted Agents And Confers Resistance To Both Targeted Drugs And Chemotherapeutics

The Heat Shock Protein of 27 kDa (HSP27) is a molecular chaperone with anti-apoptotic properties and a role in cytoskeleton stability. Not surprisingly, HSP27 is often increased in cancers and associated with poor patients' survival and resistance to conventional chemotherapy. Conversely, the role of HSP27 in response to therapies targeted towards oncogenic kinases was poorly characterized. In this chapter we review the findings on the role of HSP27 in resistance to both chemotherapeutics and targeted drugs and in the pro-metastatic phenotype, focusing on cancers where the tyrosine kinase receptor encoded by the MET oncogene is activated, namely, gastric and ovarian cancers. The inhibition of the MET receptor kinase in the MET addicted gastric cancer cells triggered HSP27 increase in a MEK/ERK dependent manner and in turn limited the effectiveness of inhibitors both in vitro and in vivo. Furthermore, in ovarian cancer cells HSP27 is required for metastasis upon MET activation in vivo and modulates the sensitivity to the first line chemotherapeutics Cisplatin and Paclitaxel. Altogether, these findings suggested that HSP27 induction by targeted agents might impact the success of targeted and conventional therapies and that it might be a suitable therapeutic target in combination treatments.