Endothelin Signaling as Target for Anticancer Therapy: from Prostate Cancer to Multiple Myeloma
Journal Title: Journal of Oncology and Cancer Research - Year 2018, Vol 2, Issue 1
Abstract
Neuropeptides including endothelin 1 (ET-1) are potent mitogens for both benign and malignant cells through G-protein receptor binding and signal transduction [1]. Aberrant expression of several components of the endothelin axis, including ET-1 and its receptors, ET-A and ET-B is found in various malignancies, including prostate cancer (PC) [1]. Evidence of increased paracrine and autocrine signaling through the endothelin axis in PC cells has triggered clinical testing of ET-1 receptor inhibitors. However, lack of clinical benefit has prevented further development of this approach [2-5]. At the cellular level, we previously reported ET-induced upregulation of proteasome activity and associated proliferative and antiapoptotic effects in androgen-independent PC cells [6]. These effects were reversed with the use of the proteasome inhibitor bortezomib [7]. However, bortezomib failed to demonstrate clinical activity in PC patients, thus its clinical use for inhibiting the endothelin axis could not be supported in that setting [8-11].
Authors and Affiliations
Panagiotis J. Vlachostergios
Keywords
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- EP ID EP274751
- DOI 10.28967/jocr.2018.01.18001
- Views 102
- Downloads 0
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