Hsp90 – a Target for Anticancer Therapy
Authors:
E. Růčková; P. Müller; B. Vojtěšek
Authors‘ workplace:
Masarykův onkologický ústav, Brno
Published in:
Klin Onkol 2011; 24(5): 329-337
Category:
Reviews
Overview
Molecular chaperones help other proteins to achieve and maintain their proper conformation. Chaperones bind to newly synthesized or unfolded polypeptide chains, actively modify their conformation and participate on their transport or degradation. Chaperones play an important role in cancer cell, where their increased activity enables stabilization of many mutant proteins and overcoming the stress generated by genetic instability. Hsp90 represents a key chaperone in cancer cells. Growth factor receptors, steroid hormone receptors and signal proteins are among its substrates, so-called client proteins; many of them being targets for anti-cancer therapy. Adverse conditions of the tumor microenvironment, such as hypoxia and nutrient deficiency, contribute to destabilization of proteins and further escalate dependence on chaperones. This is why molecular chaperones, in particular Hsp90, may represent a promising target for anticancer therapy. Importantly also, tumour-based Hsp90 has a significantly higher sensitivity to inhibitors than that in normal cells, and Hsp90 activity inhibition in tumours leads to a suppression of cellular signaling in many different oncogenic pathways. Several inhibitors of Hsp90 are currently undergoing clinical evaluation and new agents with different mechanisms of action are continually being identified.
Key words:
molecular chaperones – Hsp90 – cancer – therapy
This work was supported by grants of MZCR NS/9812-4 and RECAMO CZ.1.05/2.1.00/03.0101.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Submitted:
18. 4. 2011
Accepted:
25. 5. 2011
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