The endothelin axis in cancer: the promise and the challenges of molecularly targeted therapyThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

Author:

Bagnato Anna1,Spinella Francesca1,Rosanò Laura1

Affiliation:

1. Molecular Pathology and Ultrastructure Laboratory, Regina Elena Cancer Institute, Via delle Messi d’Oro 156, Rome 00158, Italy.

Abstract

The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and 2 G protein-coupled receptor subtypes, ETAR and ETBR, promotes growth and progression of a variety of tumors, such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast, lung, bladder, endometrial carcinoma, Kaposi’s sarcoma, brain tumors, and melanoma. Acting on selective receptors, ET-1 regulates mitogenesis, cell survival, angiogenesis, bone remodeling, stimulation of nociceptors, tumor-infiltrating immune cells, epithelial-to-mesenchymal transition, invasion, and metastatic dissemination. At the molecular level, endothelin receptor antagonists, besides providing ideal tools for dissecting the ET axis, have demonstrated their potential in developing novel therapeutic strategies. Emerging experimental and clinical data demonstrate that interfering with endothelin receptors provides an opportunity for the development of rational combinatorial approaches using endothelin receptor antagonists in combination with chemotherapy or molecularly targeted therapy.

Publisher

Canadian Science Publishing

Subject

Physiology (medical),Pharmacology,General Medicine,Physiology

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