HSP90 and Its Inhibitors for Cancer Therapy: Use of Nano-delivery System to Improve Its Clinical Application

Abstract

The molecular chaperone HSP90 (heat shock protein 90) has become a crucial target in cancer therapeutics as its function has been implicated with various types of malignant transformation. Numerous HSP90 inhibitors have been identified so far and many of them have also been clinically tested. Although most of these are natural or their derived inhibitors including geldanamycin and its derivatives 17-AAG and 17-DMAG have shown efficacy, their easy success has been hindered in various stages of the clinical studies due to poor solubility and cytotoxicity. However, recently substantial published documents reported that the systemic targeting of the HSP90 inhibitors using nano-based drug delivery system could provide a possible clinical solution to overcome their limitation. In this chapter, we review the initial development of various HSP90 inhibitors from natural to synthetically derived one and their clinical studies. We also review their limitations and future perspectives as a possible potential agent in the cancer therapeutics by their systemic and control delivery to the target site using the nano-drug delivery system. Also, the application of combined therapy has also been discussed in the current chapter using HSP90 inhibitors and nanocarrier. In addition, we also discuss the therapeutic approaches like photothermal where nano carrier is not only used as a carrier for the systemic delivery of HSP90 inhibitors but also as a therapeutic agent.