Hypothesis: Cancer Hormesis and Its Potential for Cancer Therapeutics.

Abstract

Primary tumors can inhibit the growth of secondary lesions, particularly metastases, in a phenomenon termed "concomitant resistance". Several mechanisms have been proposed for this effect, each supported by experimental data. In this paper, we hypothesize that concomitant resistance is a form of hormesis, a biphasic dose response in which a stimulus has a positive and/or stimulatory effect at low dosages and a negative, inhibitory, and/or toxic effect at higher dosages. When this paradigm applies to tumorigenesis, it is referred to as "cancer hormesis". Thus, low numbers of benign neoplastic cells or less tumorigenic malignant cells may result in resistance to the development of malignant neoplasms, including metastases. A host containing a number of (less tumorigenic) neoplastic cells may exhibit greater protection against more tumorigenic malignant neoplasms than a host who lacks neoplastic cells, or who has too few neoplastic cells to stimulate a protective response. As a theoretical endeavor, this paper also proposes that cancer hormesis can be leveraged for therapeutic purposes, by the implantation of safely controlled, benign artificial tumors in high-risk patients. These tumors would prevent the development of endogenous malignant neoplasms by creating an inhibitory environment for such growth. Strategies for testing the hypothesis are proposed.