Epigenetic mediators were developed as new targets for cancer drugs recently. It is the first time CDK9 has been linked to gene silencing in mammals.
Jean-Pierre Issa, MD, Director of the Fels Institute for Cancer Research & Molecular Biology at the Lewis Katz School of Medicine at Temple University (LKSOM), led the research. The paper appears in the journal Cell,
‘CDK9 inhibitor is highly beneficial and safe to treat patients suffering from cancer.’
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."