Engineering Multidimensional Evolutionary Forces to Combat Cancer.

Authors:
Caroline E McCoach
Caroline E McCoach
University of California
United States
Trever G Bivona
Trever G Bivona
New York University School of Medicine

Cancer Discov 2019 May 16;9(5):587-604. Epub 2019 Apr 16.

Department of Medicine, University of California, San Francisco, California.

With advances in technology and bioinformatics, we are now positioned to view and manage cancer through an evolutionary lens. This perspective is critical as our appreciation for the role of tumor heterogeneity, tumor immune compartment, and tumor microenvironment on cancer pathogenesis and evolution grows. Here, we explore recent knowledge on the evolutionary basis of cancer pathogenesis and progression, viewing tumors as multilineage, multicomponent organisms whose growth is regulated by subcomponent fitness relationships. We propose reconsidering some current tenets of the cancer management paradigm in order to take better advantage of crucial fitness relationships to improve outcomes of patients with cancer. SIGNIFICANCE: Tumor and tumor immune compartment and microenvironment heterogeneity, and their evolution, are critical disease features that affect treatment response. The impact and interplay of these components during treatment are viable targets to improve clinical response. In this article, we consider how tumor cells, the tumor immune compartment and microenvironment, and epigenetic factors interact and also evolve during treatment. We evaluate the convergence of these factors and suggest innovative treatment concepts that leverage evolutionary relationships to limit tumor growth and drug resistance.

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Source
http://cancerdiscovery.aacrjournals.org/lookup/doi/10.1158/2
Publisher Site
http://dx.doi.org/10.1158/2159-8290.CD-18-1196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497542PMC
May 2019
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