It is well-recognized that the majority of
cancer-related deaths is attributed to
metastasis, which can arise from virtually any type of
tumor.
Metastasis is a complex multistep process wherein
cancer cells must break away from the primary
tumor, intravasate into the circulatory or lymphatic systems, extravasate, proliferate and eventually colonize secondary sites. Since these molecular processes involve the coordinated actions of numerous
proteins, targeted disruptions of key players along these pathways represent possible therapeutic interventions to impede
metastasis formation and reduce
cancer mortality. A diverse group of
proteins with demonstrated ability to inhibit metastatic colonization have been identified and they are collectively known as
metastasis suppressors. Given that the
metastasis suppressors are often downregulated in
tumors, drug-induced re-expression or upregulation of these
proteins represents a promising approach to limit
metastasis. Indeed, over 40 compounds are known to exhibit efficacy in upregulating the expression of
metastasis suppressors via transcriptional or post-transcriptional mechanisms, and the most promising ones are being evaluated for their translational potentials. These small molecules range from natural products to drugs in clinical use and they apparently target different molecular pathways, reflecting the diverse nature of the
metastasis suppressors. In this review, we provide an overview of the different classes of compounds known to possess the ability to upregulate one or more
metastasis suppressors, with an emphasis on their mechanisms of action and therapeutic potentials.