Therapeutic YY1 Inhibitors in Cancer: ALL in ONE

Various targeted therapies for cancer have resulted in a significant prolongation of survival and a better quality of life. However, unfortunately, a small subset of cancer patients responds to such therapies initially and then develops resistance after the initial therapies. Based on resistant mechanisms, it should be possible to develop new and specific targeted therapies effective against unresponsive patients. Our investigations and those of others have identified a gene product, Yin Yang 1 (YY1), a transcription factor that is overexpressed in many cancers and that was shown to be involved in the regulation of cell survival, cell proliferation, cell invasion, metastasis, and resistance. Several studies showed that the inhibition of YY1 resulted in significant inhibition of the tumor phenotype and reversal of resistance. Examples of such YY1 inhibitors include siRNA YY1, nitric oxide donors, proteasome inhibitors, and inhibitors of activated survival pathways such as inhibitors of nuclear factor-kappa beta. However, there is still a need to develop specific and targeted inhibitors of YY1. In this review, a general discussion is provided on the role of YY1 overexpression in cancer and the application of various inhibitors of YY1 activities and their potential as therapeutics.