A Review of Two Promising Radiosensitizers in Brain Metastases: Rrx-001 and 2-Deoxyglucose
|Bryan T. Oronsky1* , Neil C. Oronsky2, Gary R. Fanger1, Arnold L. Oronsky3, Michelle M.C. Lybeck1, Harry E. Lybeck4, Scott Z. Caroen1, Christopher W. Parker1 and Jan Scicinski1|
|1EpicentRx Inc, 800 W El Camino Real, Suite 180, Mountain View, CA 94040, USA|
|2CFLS, LLC, 560 South Winchester Boulevard, San Jose, CA 95128, USA|
|3InterWest Partners, 2710 Sand Hill Road #200, Menlo Park, CA 94025, USA|
|4Helsinki University, Yliopistonkatu 4, 00100 Helsinki, Finland|
|Corresponding Author :||Bryan T. Oronsky
EpicentRx Inc, 800 W El Camino Real
Suite 180, Mountain View
CA 94040, USA
Tel: (408) 569 3202
E-mail: [email protected]
|Received March 01, 2015; Accepted April 24, 2015; Published April 27, 2015|
|Citation: Oronsky BT, Oronsky NC, Fanger GR, Oronsky AL, Lybeck MMC, et al. (2015) A Review of Two Promising Radiosensitizers in Brain Metastases: Rrx-001 and 2-Deoxyglucose. J Cancer Sci Ther 07:137-141. doi:10.4172/1948-5956.1000338|
|Copyright: © 2015 Oronsky BT, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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The origin of the common phrase “your name is mud” may derive from the ordeal of 19th century physician, Dr. Samuel Mudd, who was perhaps wrongly convicted of conspiracy in the assassination of President Abraham Lincoln. Mudd’s crime may have only been bad luck: Lincoln’s assassin, John Wilkes Booth, allegedly previously unknown to the doctor, had broken his leg and happened across Mudd who, unwisely, as it turned out, set the fracture, and his own subsequent fate, which included life imprisonment with hard labor, making him a potential victim of circumstance rather than the perpetrator of a crime. Mudd’s grandson, also a physician, tried unsuccessfully to clear his grandfather’s widely reviled name, which as a result has remained, both literally and figuratively, Mudd.
This historical analogy highlights the important point that radiosensitizers as a class have been ignored rather than adored due to their failed reputation. Hence, in the field of radiation oncology, the “your name is mud” expression applies to radiation sensitizers, which from hyperbaric oxygen and the nitroimidazoles, to motexafin gadolinium, tirapazamine and efaproxiral have generally overpromised and under delivered with respect to survival treatment benefits in multiple different indications. However, newer non-toxic radiosensitizers on the horizon such as the antienergetic epigenetic redox modulator, RRx-001, that will start a Phase 2 clinical trial with concurrent whole brain radiotherapy (WBRT) in subjects with brain metastases, may finally validate the underlying promise and unrealized potential of these agents. The successful treatment of brain metastases is at least a four-hurdle process involving penetration, retention, selectivity and toxicity. This article will review the mechanism of the radiosensitizers, RRx- 001, and 2-deoxyglucose, as examples or “role models” for therapies that theoretically are able to overcome these substantial in vivo obstacles to successfully treat brain metastases.
It is the thesis of this review that new radiosensitizers are urgently needed and their poor reputation should be overcome.