RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials
RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials
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DOI：
10.1080/13543784.2017.1268600
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发表时间：
2017-01-01
影响因子：
6.1
通讯作者：
Carterg, Corey A.
中科院分区：
文献类型：
--
作者：
Oronsky, Bryan;Paulmurugan, Ramasamy;Carterg, Corey A.
简介：根据Hanahan和温伯格，癌症表现为六个基本的生理标志：（1）生长信号的自给自足，（2）对生长抑制信号不敏感，（3）逃避程序性细胞死亡，（4）无限的复制潜力，（5）持续的血管生成，和（6）侵袭和转移。作为这些特征以及免疫抑制和化学抗性的促进者，肿瘤相关巨噬细胞（TAM）的存在可能是癌症的第七个标志。成功地将TAM重编程为靶向而非支持肿瘤细胞的抗癌药物可能是获得更好治疗结果的关键。本文总结了巨噬细胞刺激剂RRx-001的特性，RRx-001是一种分子破坏者，来源于航空航天工业，特别强调细胞间转移的作用机制（从红细胞到药物）是其抗肿瘤活性及其化疗和放射防护特性的基础，这些特性已从各种临床前和临床研究中得到巩固。专家意见：RRx-001是巨噬细胞刺激剂，具有与化疗、放疗和免疫治疗协同作用的潜力，同时保护正常组织免受其细胞毒性作用。鉴于在多种肿瘤类型中的活性的有希望的适应症和这些正常组织保护特性，如果将来获得批准，RRx-001可用于治疗广谱恶性肿瘤。
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.