Endothelin receptor antagonism and cancer

Authors

Errata

This article is corrected by:

  1. Errata: Erratum Volume 39, Issue 7, 630, Article first published online: 5 June 2009

  • This paper forms part of the supplement entitled ‘Update on endothelin-related diseases’. It is related to discussions at the workshop ‘Endothelin-related diseases’ at 42nd Annual Scientific Meeting of the European Society for Clinical Investigation (ESCI) in Geneva, Switzerland, 26–29 March 2008. The workshop and the production costs of the present supplement were supported with an unrestricted Educational Grant from Encysive Pharmaceuticals Inc. In June 2008, Encysive was acquired by Pfizer Inc who funded the publication and formatting costs of this supplement. Tracy Johnson formatted the manuscript according to the journal’s style requirements.

Abstract

The endothelin peptides have an important role in the cancer-stromal interactions that promote tumour growth. Endothelin-1 (ET-1), clinically the most investigated endothelin, is a vital agent in the growth and progression of several tumours including prostate, ovarian, colorectal, bladder, breast and lung carcinomas. ET-1 exerts its effects through the activation of two distinct receptors, ETA and ETB. Once activated, these receptors transmit signals via numerous intracellular signalling pathways. The effects of ET receptor stimulation in cancer cells or cancer-associated cells include proliferation, resistance to apoptosis, angiogenesis, migration and subsequent invasion. At present, the manipulation of the endothelin axis within the pre-clinical setting is the subject of intense investigation. Recent studies into ET receptor antagonism have produced interesting results highlighting the fact that these receptors may provide novel targets for a new generation of chemotherapeutic agents in a variety of cancers.

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