This Article Full Text Full Text (PDF) All Versions of this Article: 0008-5472.CAN-09-1354v1 69/19/7499    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gatenby, R. A. Articles by Vincent, T. PubMed PubMed Citation Articles by Gatenby, R. A. Articles by Vincent, T.

Lessons from Applied Ecology: Cancer Control Using an Evolutionary Double Bind

¹ Departments of Radiology and Integrative Mathematical Oncology, Moffitt Cancer Center, Tampa, Florida; ² Department of Ecology and Evolutionary Biology, University of Illinois, Chicago, Illinois; and ³ Department of Aerospace Engineering, University of Arizona, Tucson, Arizona

Requests for reprints: Robert A. Gatenby, Department of Radiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612. Phone: 813-745-2843; Fax: 813-745-6070; E-mail: Robert.Gatenby{at}Moffitt.org.

Abstract

Because the metastatic cascade is largely governed by the ability of malignant cells to adapt and proliferate at the distant tissue site, we propose that disseminated cancers are analogous in many important ways to the evolutionary and ecological dynamics of exotic species. Although pests can be decimated through the application of chemical toxins, this strategy virtually never achieves robust control as evolution of resistant phenotypes typically permits population recovery to pretreatment levels. In general, biological strategies that introduce predators, parasitoids, or pathogens have achieved more durable control of pest populations even after emergence of resistant phenotypes. From this we propose that long term outcome from any treatment strategy for invasive pests, including cancer, is not limited by evolution of resistance, but rather by the phenotypic cost of that resistance. If a cancerous cell's adaptation to therapy is achieved by upregulating xenobiotic metabolism or a redundant signaling pathway, the required investment in resources is small, and the original malignant phenotype remains essentially intact. As a result, the cancer cells' initial high level of fitness is little changed and unconstrained proliferation will resume once resistance evolves. Robust population control is possible if resistance to therapy requires a substantial and costly phenotypic adaptation that also significantly reduces the organism's fitness in its original niche: an evolutionary double bind. [Cancer Res 2009;69(19):7499–502]