PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities

The epigenetic regulation of gene functions has been proven to be strongly associated with the development and progression of cancer. Reprogramming the cancer epigenome landscape is one of the most promising target therapies in both treatments and in reversing drug resistance. Proteolytic targeted chimeras (PROTACs) are an emerging therapeutic modality for selective degradation via the native ubiquitin-proteasome system. Rapid advances in PROTACs have facilitated the exploration of targeting epigenetic proteins, a lot of PROTAC degraders have already been designed in the field of epigenetic cancer therapy, and PROTACs targeting epigenetic proteins can better exploit target druggability and improve the mechanistic understanding of the epigenetic regulation of cancer. Thus, this review focuses on the progress made in the development of PROTAC degraders and PROTAC drugs targeting epigenetics in cancer and discusses challenges and future opportunities for the field.

Automated summary

The epigenetic regulation of gene functions is closely associated with cancer development and progression. Reprogramming the cancer epigenome landscape is a promising target therapy for treating cancer and reversing drug resistance. Proteolytic targeted chimeras (PROTACs) are emerging therapeutic modality that selectively degrade proteins via the ubiquitin-proteasome system. Many PROTAC degraders have been designed in the field of epigenetic cancer therapy, and targeting epigenetic proteins with PROTACs can enhance target druggability and improve mechanistic understanding of cancer epigenetic regulation. This review focuses on the progress in developing PROTAC degraders and PROTAC drugs targeting epigenetics in cancer, and discusses challenges and future opportunities for this field.