May 27th 2010
£295 / $515 / €365
Online, PDF
The potential of Heat Shock Proteins (HSPs) has sparked considerable research and industry interest. Results from early phase studies are encouraging — are they the next big thing in cancer therapy?
Heat shock proteins have emerged as a promising target for cancer therapy and Espicom has identified a number of projects currently under clinical investigation that span both Phase I and II clinical trials. The majority of agents progressing through development are HSP90 inhibitors, with one HSP-based anticancer vaccine.
As a chaperone protein, HSP90 plays an important role in regulating the function and activity of numerous clients, or signalling, proteins that have been shown to be critical to cancer cell growth, proliferation and survival. The inhibition of HSP90 leads to degradation of these client proteins and the subsequent death of cancer cells dependent on their activity.
Many of HSP90’s client proteins are the targets of existing cancer drugs such as Roche’s Avastin (bevacizumab), Herceptin (trastuzumab) and Tarceva (erlotinib), Novartis’ Gleevec/Glivec (imatinib), Bayer’s Nexavar (sorafenib) and Pfizer’s Sutent (sunitinib). Inhibiting HSP90 offers the potential for treating cancers that have become resistant to targeted therapies such as the kinase inhibitors, for even kinase inhibitors are still dependent on HSP90 for their activity. The early HSP90 inhibitors, as analogues of geldanamycin, showed promising antitumour activity but were dogged by drug-related toxicities including hepatotoxicity, nephrotoxicity and pancreatitis, plus poor solubility, metabolic stability and difficulty in administration. Hence, few remain in clinical development.
The majority of HSP90 inhibitors now progressing through clinical trials are fully-synthetic compounds, with a number offering the advantage of oral availability. Assuming continued successful development, Biogen Idec’s synthetic, oral HSP90 inhibitor, BIIB021, looks set to be the first HSP inhibitor to reach the market in 2014, with potential future competition from other oral synthetic agents namely, Debio 0932, HSP990, MPC-3100, PF-04929113 and XL888, all currently progressing through Phase I trials.
This executive briefing provides a complete, fast, easy-to-read overview of the promising
and topical Heat Shock Protein sector
EXECUTIVE SUMMARY
Introduction
What are Heat Shock Proteins?
Applications of Heat Shock Proteins
Research and Development Projects
Discontinued Development Projects
Summary
PRODUCTS UNDER PHASE II DEVELOPMENT
The following products are assessed by Mode of Action, Current Status, Proof of Concept/Clinical Data, Development Risks, Company Expertise, Competition within the Marketplace and Competitor Ratio Analysis
PRODUCTS UNDER PHASE I DEVELOPMENT
Heat Shock Protein 90 Inhibitors
Heat Shock Protein 27 Inhibitor
This product is assessed by Mode of Action, Current Status, Proof of Concept/Clinical Data, Development Risks, Company Expertise, Competition within the Marketplace and Competitor Ratio Analysis
APPENDIX 1: PHASE TRANSITION PROBABILITY
APPENDIX 2: GLOSSARY
APPENDIX 3: BIBLIOGRAPHY