Therapeutic targeting of SNAIL, RKIP, and YY1 in tumor metastasis and drug resistance

Abstract Cancer is the leading cause of deaths worldwide and is of great importance. Metastasis-inducing the majority of cancer related deaths is a principal problem in cancer treatment. Therefore, therapy regimes preventing metastasis formation are of prominent importance to improve the outcome of malignant diseases. The epithelial-mesenchymal transition (EMT) is a predominant process associated with the onset of metastasis and converts epithelial cells to mesenchymal cells. In this chapter, we concentrated on three proteins involved in the metastasis and EMT: RKIP, SNAIL, and YY1. Briefly, SNAIL and YY1 are overexpressed in many cancers, while RKIP is downregulated. Therefore, these proteins may serve as therapeutic targets to suppress tumor metastasis. We describe herein synthetic small molecules as modulators of these three proteins. Because a majority of the clinically established anticancer drugs during the past half century are of natural origin or are derivatives thereof, we have also included chemical entities isolated from medicinal plants and phytotherapeutic preparations involved in the regulation of SNAIL, RKIP, and YY1. Natural products may serve as scaffolds for further chemical derivatization to develop novel drug candidates to fight the metastatic process.