Abstract
Since the identification of NM23 (now called NME1) as the first metastasis suppressor gene (MSG), a small number of other gene products and non-coding RNAs have been identified that suppress specific parameters of the metastatic cascade, yet which have little or no ability to regulate primary tumor initiation or maintenance. MSG can regulate various pathways or cell biological functions such as those controlling mitogen-activated protein kinase pathway mediators, cell–cell and cell-extracellular matrix protein adhesion, cytoskeletal architecture, G-protein-coupled receptors, apoptosis, and transcriptional complexes. One defining facet of this gene class is that their expression is typically downregulated, not mutated, in metastasis, such that any effective therapeutic intervention would involve their re-expression. This review will address the therapeutic targeting of MSG, once thought to be a daunting task only facilitated by ectopically re-expressing MSG in metastatic cells in vivo. Examples will be cited of attempts to identify actionable oncogenic pathways that might suppress the formation or progression of metastases through the re-expression of specific metastasis suppressors.
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Funding
This work was supported by grants R21-CA235092 (NCI) and W81XWH-20-BCRP-BTA12-2 (DOD) to I.H.G. and by the P30-CA016056 (NCI) Comprehensive Cancer Center grant.
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Gelman, I.H. Metastasis suppressor genes in clinical practice: are they druggable?. Cancer Metastasis Rev 42, 1169–1188 (2023). https://doi.org/10.1007/s10555-023-10135-w
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DOI: https://doi.org/10.1007/s10555-023-10135-w