CDK9 inhibition appears to be an excellent target for epigenetic cancer therapy. Genes that have been epigenetically silenced by cancer can be reactivated by inhibiting CDK9, a DNA transcription regulator.
It has been established that epigenetic mediators of gene silencing present new targets for cancer drugs. Hanghang Zhang, PhD, of the Fels Institute for Cancer Research & Molecular Biology at LKSOM, the first author on the report, performed a live cell drug screen with genetic confirmation to identify CDK9 as a target and to develop and test an effective inhibitor - MC180295.
The new drug is highly selective, potentially avoiding the side effects associated with inhibiting the cell cycle. In the study, it showed broad effectiveness against cancer both in vitro and in vivo. The drug was discovered in collaboration with investigators at the Moulder Center for Drug Discovery at the Temple University School of Pharmacy.
"In addition to reactivating tumor suppressor genes, CDK9 inhibition induces sensitivity to the immune checkpoint inhibitor α-PD-1 in vivo," said Issa. "It is an excellent target for epigenetic cancer therapy."
Source-Eurekalert
