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Metastasis-suppressor genes in clinical practice: lost in translation?

Abstract

Over the past 25 years, an expanding set of metastasis-suppressor genes (MSGs) has been identified that specifically regulate metastasis formation without affecting primary growth. MSGs are involved in diverse molecular processes in multiple tumor types. Given the wealth of metastasis biology that underlies their functions, treatment strategies based on MSGs have an unparalleled potential to improve patient care. Using NM23 as a prime example, we discuss how specific MSGs have been used as prognostic markers, tools for predicting response to treatment, and targets for the development of novel therapies. Barriers specific to the translation of MSG biology into clinical practice are reviewed and future research directions necessary for clinical advances are delineated. Although to date the impact of MSGs on patient care is limited, it is an expanding field with vast potential to help develop new treatments and identify patients who will most benefit from them.

Key Points

  • The discovery of metastasis-suppressor genes (MSGs) has underscored the importance of understanding mechanisms of the metastatic process

  • Numerous human studies have identified specific MSGs with prognostic importance in multiple independent tumor types

  • Preclinical data and retrospective human studies suggest that MSGs have the potential to improve patient selection and prediction of response to treatment

  • Mechanistic insights into MSG function have led to the development of novel treatment strategies targeting metastatic disease; clinical trials using the MSG NM23 as an antimetastatic therapy are underway

  • There is a critical need for additional prospective clinical and translational studies that test the ability of MSGs to predict and treat metastatic disease

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Figure 1: Proposed mechanisms for metastasis suppression by PEBP1, RECK, and CTGF in colon cancer.

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Acknowledgements

This work was supported by grants to the authors: DOD Ovarian Cancer W81XWH-09-1-0127 and DOD Prostate Cancer W81XWH-09-1-0449 (C. W. Rinker-Schaeffer), NIH 5RO1 CA089569 and DOD Prostate Cancer Physician Research Training Award W81XWH-09-1-0415 (R. Z. Szmulewitz). C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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A. N. Shoushtari and R. Z. Szmulewitz researched the data and wrote the manuscript. All authors were involved in discussing the article content and revising the manuscript throughout the submission process.

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Correspondence to Carrie W. Rinker-Schaeffer.

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Shoushtari, A., Szmulewitz, R. & Rinker-Schaeffer, C. Metastasis-suppressor genes in clinical practice: lost in translation?. Nat Rev Clin Oncol 8, 333–342 (2011). https://doi.org/10.1038/nrclinonc.2011.65

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