Endothelin receptor antagonism and cancer.
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, ET(A) and ET(B). 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.
Bhalla
A
A
UCL Medical School, London, UK.
Haque
S
S
Taylor
I
I
Winslet
M
M
Loizidou
M
M