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Dormancy in solid tumors: implications for prostate cancer

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Abstract

In cancer dormancy, residual tumor cells persist in a patient with no apparent clinical symptoms, only to potentially become clinically relevant at a later date. In prostate cancer (PCa), the primary tumor is often removed and many patients experience a prolonged period (>5 years) with no evidence of disease before recurrence. These characteristics make PCa an excellent candidate for the study of tumor cell dormancy. However, the mechanisms that constitute PCa dormancy have not been clearly defined. Additionally, the definition of tumor cell dormancy varies in the literature. Therefore, we have separated tumor cell dormancy in this review into three categories: (a) micrometastatic dormancy—a group of tumor cells that cannot increase in number due to a restrictive proliferation/apoptosis equilibrium. (b) Angiogenic dormancy—a group of tumor cells that cannot expand beyond the formation of a micrometastasis due to a lack of angiogenic potential. (c) Conditional dormancy—an individual cell or a very small number of cells that cannot proliferate without the appropriate cues from the microenvironment, but do not require angiogenesis to do so. This review aims to identify currently known markers, mechanisms, and models of tumor dormancy, in particular as they relate to PCa, and highlight current opportunities for advancement in our understanding of clinical cancer dormancy.

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Abbreviations

CRPC:

Castration-resistant prostate cancer

CTC:

Circulating tumor cell

DTC:

Disseminated tumor cells

PCa:

Prostate cancer

PSA:

Prostate-specific antigen

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Acknowledgments

This material is the result of work supported by the NIH RC1 CA144825 ARRA challenge award, NIH P01 CA085859, a sponsored research agreement with Jenssen Pharmaceuticals Inc. and the VA Puget Sound Health Care System, Seattle, WA, USA (RLV is a Research Career Scientist, PHL is a Staff Physician).

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Correspondence to Robert L. Vessella.

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Ruppender, N.S., Morrissey, C., Lange, P.H. et al. Dormancy in solid tumors: implications for prostate cancer. Cancer Metastasis Rev 32, 501–509 (2013). https://doi.org/10.1007/s10555-013-9422-z

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