Brief report: RRx-001 is a c-Myc inhibitor that targets cancer stem cells
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Bryan Oronsky1, Tony R. Reid2, Arnold Oronsky3, Scott Caroen1, Corey A. Carter1 and Pedro Cabrales4
1EpicentRx Inc, San Diego, CA 92121, USA
2Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
3InterWest Partners, Menlo Park, CA 94025, USA
4Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
Bryan Oronsky, email: [email protected]
Keywords: cancer stem cell; c-Myc; Wnt pathway; RRx-001; resistance reversal
Received: March 20, 2018 Accepted: April 08, 2018 Published: May 04, 2018
The goal of anticancer therapy is to selectively eradicate all malignant cells. Unfortunately for the majority of patients with metastatic disease, this goal is consistently thwarted by the nearly inevitable development of therapeutic resistance; the main driver of therapeutic resistance is a minority subpopulation of cancer cells called cancer stem cells (CSCs) whose mitotic quiescence essentially renders them non-eradicable. The Wnt signaling pathway has been widely implicated as a regulator of CSCs and, therefore, its inhibition is thought to result in a reversal of therapeutic resistance via loss of stem cell properties.
RRx-001 is a minimally toxic redox-active epi-immunotherapeutic anticancer agent in Phase III clinical trials that sensitizes tumors to radiation and cytotoxic chemotherapies. In this article, as a potential mechanism for its radio- and chemosensitizing activity, we report that RRx-001 targets CD133+/CD44+ cancer stem cells from three colon cancer cell-lines, HT-29, Caco-2, and HCT116, and inhibits Wnt pathway signalling with downregulation of c-Myc.
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