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Int. J. Mol. Sci. 2017, 18(6), 1258;

Deconstructing Signaling Pathways in Cancer for Optimizing Cancer Combination Therapies

Department of Anesthesia, Kansai Medical University, Hirakata, Osaka 573-1010, Japan
National Center for Microscopy and Imaging Research, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 27 April 2017 / Revised: 27 May 2017 / Accepted: 5 June 2017 / Published: 12 June 2017
(This article belongs to the Special Issue Alterations to Signalling Pathways in Cancer Cells)
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A single cancer cell left behind after surgery and/or chemotherapy could cause a recurrence of cancer. It is our belief that the failure of chemotherapies is the failure to induce apoptosis in all cancer cells. Given the extraordinary heterogeneity of cancer, it is very difficult to eliminate all cancer cells with a single agent targeting a particular gene product. Furthermore, combinations of any two or three agents exhibiting some proven efficacy on a particular cancer type have not fared better, often compounding adverse effects without evidence of expected synergistic effects. Thus, it is imperative that a way be found to select candidates that when combined, will (1) synergize, making the combination therapy greater than the sum of its parts, and (2) target all the cancer cells in a patient. In this article, we discuss our experience and relation to current evidence in the cancer treatment literature in which, by deconstructing signaling networks, we have identified a lynchpin that connects the growth signals present in cancer with mitochondria-dependent apoptotic pathways. By targeting this lynchpin, we have added a key component to a combination therapy that sensitizes cancer cells for apoptosis. View Full-Text
Keywords: combination therapy; lynchpin; signal transduction; apoptosis; VHL; PI3K; AKT combination therapy; lynchpin; signal transduction; apoptosis; VHL; PI3K; AKT

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Yamaguchi, R.; Perkins, G. Deconstructing Signaling Pathways in Cancer for Optimizing Cancer Combination Therapies. Int. J. Mol. Sci. 2017, 18, 1258.

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