Tumors are like new organs and are made of multiple cell types and components. The tumor competes with the normal microenvironment to overcome antitumorigenic pressures. Before that battle is won, the tumor may exist within the organ unnoticed by the host, referred to as 'occult cancer'. We review how normal tissue homeostasis and architecture inhibit progression of cancer and how changes in the microenvironment can shift the balance of these signals to the procancerous state. We also include a discussion of how this information is being tailored for clinical use.
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We thank C. Ghajar for considerable help for the background materials and him, J. Mott and I. Kuhn for critical reading of the manuscript. We also thank K. Andersen, D. Lyden, S. Rafii, M. de Sousa and M.H. Barcellos-Hoff for referring us to clinically related articles qualifying as 'microenvironmental therapy'. We thank M. Bisoffi for providing the full-text versions of articles on the occult tumors in the prostate and E. Collisson for directing us to references on occult tumors of the pancreas. The work from M.J.B.'s laboratory is supported by grants from the US Department of Energy, Office of Biological and Environmental Research and Low Dose Radiation Program (contract no. DE-AC02-05CH1123), by the US National Cancer Institute (awards R37CA064786, U54CA126552, R01CA057621, U54CA112970, U01CA143233 and U54CA143836—Bay Area Physical Sciences–Oncology Center, University of California–Berkeley) and by the US Department of Defense (W81XWH0810736).
The authors declare no competing financial interests.
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Bissell, M., Hines, W. Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17, 320–329 (2011). https://doi.org/10.1038/nm.2328
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