tNOX (ENOX2) Target for Chemosensitization-Low-Dose Responses in the Hormetic Concentration Range
D. James Morre, Sara Dick, Elena Bosneaga, Andrew Balicki, L.Y. Wu., Nicole McClain and Dorothy M. Morre
DOI : 10.3844/ajptsp.2008.19.29
American Journal of Pharmacology and Toxicology
Volume 3, Issue 1
An emerging concept of cancer chemotherapy is that of chemosensitization. Most often applied to the treatment of drug-resistance cancers, chemosensitization has utility when such cancers are rendered drug sensitive through treatment with the sensitizing agent. A particularly striking example of chemosensitization is that encountered with the synthetic isoflavene phenoxodiol where patients with taxane- and/or platinum-resistant ovarian carcinoma once again become sensitive to these drugs following treatment with phenoxodiol. The latter appears to be a true chemosensitization in that the phenoxodiol need not be co-administered with the taxane or platinum drugs. Sensitivity is retained many weeks after the phenoxodiol has been cleared from the system. The response appears to be mediated through the primary drug target of phenoxodiol, a cancer-specific cell surface ECTO-NOX or ENOX protein designated tNOX (ENOX2). The ENOX protein family has been previously recognized as a hormetic target. The hypothesis under investigation is that chemosensitization and low dose synergies are most obvious in the hormetic range of concentrations and that the two phenomena, hormesis and chemosensitization, may be related mechanistically.
© 2008 D. James Morre, Sara Dick, Elena Bosneaga, Andrew Balicki, L.Y. Wu., Nicole McClain and Dorothy M. Morre. 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.