RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials

Bryan Oronsky, Ramasamy Paulmurugan, Kira Foygel, Jan Scicinski, Susan J. Knox, Donna Peehl, Hongjuan Zhao, Shoucheng Ning, Pedro Cabrales, Thomas A. Summers, Tony R. Reid, William L. Fitch, Michelle M. Kim, Jane B. Trepel, Min Jung Lee, Santosh Kesari, Nacer D. Abrouk, Regina M. Day, Arnold Oronsky, Carolyn M. RayCorey A. Carterg

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

Original languageEnglish (US)
Pages (from-to)109-119
Number of pages11
JournalExpert Opinion on Investigational Drugs
Volume26
Issue number1
DOIs
StatePublished - Jan 2 2017

Keywords

  • RRx-001
  • Tumor associated macrophages
  • cancer stem cells
  • cancer therapy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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