Recent Developments in Anticancer Agents Targeting Heat Shock Proteins

Proteins are metabolic factors to perform biochemical functions. For proper protein function, these macromolecules must be in their properly folded-native states. Under stress, cells employ Heat Shock Proteins (Hsps) to overcome this folding problem. For this reason, Hsp proteins play essential roles in the metabolic processes. In cancer cells the situation is different than healthy cells. Since the metabolic rates of cancer cells are faster than that of healthy cells, cancer cells overexpress Hsps to rescue unfolded proteins to perform biochemical functions. Thus, several research groups have been focused on Hsps. This protein family consists of several members and interacts with several cell signaling proteins, kinases, and transcriptional factors. All these interactions provide key controlling points to inhibit cancer cells and drive them to apoptosis for therapeutic purposes. Different approaches on Hsp mechanism were employed for cancer cell inhibition either by interrupting Hsp90-apoptosis inhibitor protein interactions or by blocking Hsp90-proteasome function. In a similar way, topoisomerase-Hsp90 interaction was perturbed. Small molecules as well as peptides were employed to inhibit functions of Hsp70 and Hsp27. Several designs were performed and patented using Hsp cascade and this study summarizes the innovative patents in the area.

Keywords: Antigenic peptide complex, apoptosis, berberine, cancer, chimeric peptide, delivering an anticancer agent, heat shock protein targeted therapy, hepatitis, hepatoma, Hsp27, Hsp70 inhibitors, Hsp90 NTD inhibitors, Hsp90 CTD inhibitors, oncogenic client proteins, peptides, proteasome, protein folding, protein-protein interaction inhibitor, secreting modified heat shock protein, topoisomerase I.