¹Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria

Correspondence: A Villunger, Laboratory of Developmental Immunology, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria. Tel: +43-512-507-3105; Fax: +43-512-507-2867; E-mail: andreas.villunger@i-med.ac.at

Received 18 January 2006; Revised 10 March 2006; Accepted 13 March 2006; Published online 28 April 2006.

Abstract

Induction of apoptosis in tumour cells, either by direct activation of the death receptor pathway using agonistic antibodies or recombinant ligands, or direct triggering of the Bcl-2-regulated intrinsic apoptosis pathway by small molecule drugs, carries high hopes to overcome the shortcomings of current anticancer therapies. The latter therapy concept builds on a more detailed understanding of how Bcl-2-like molecules maintain mitochondrial integrity and how BH3-only proteins and Bax/Bak-like molecules can undermine it. Means to unleash the apoptotic potential of BH3-only proteins in tumour cells, or bypass the need for BH3-only proteins by blocking possible interactions of Bcl-2-like prosurvival molecules with Bax and/or Bak allowing their direct activation, constitute interesting options for the design of novel anticancer therapies.