New epigenetic drug strategy to treat cancer

Researchers have discovered that inhibiting CDK9, a DNA transcription regulator, reactivates genes that have been epigenetically silenced by cancer. Reactivation leads to restored tumor suppressor gene expression and enhanced anti-cancer immunity. It is the first time this particular kinase 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.

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."

Hanghang Zhang, Somnath Pandey, Meghan Travers, Hongxing Sun, George Morton, Jozef Madzo, Woonbok Chung, Jittasak Khowsathit, Oscar Perez-Leal, Carlos A. Barrero, Carmen Merali, Yasuyuki Okamoto, Takahiro Sato, Joshua Pan, Judit Garriga, Natarajan V Bhanu, Johayra Simithy, Bela Patel, Jian Huang, Noël J-M Raynal, Benjamin A Garcia, Marlene A Jacobson, Cigall Kadoch, Salim Merali, Yi Zhang, Wayne Childers, Magid Abou-Gharbia, John Karanicolas, Stephen B Baylin, Cynthia A Zahnow, Jaroslav Jelinek, Xavier Graña, Jean-Pierre J Issa.
Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer.
Cell, October 25, 2018. doi: 10.1016/j.cell.2018.09.051.

Most Popular Now

Novartis receives FDA approval for Mayzent® (sipon…

Novartis today announced that the US Food and Drug Administration (FDA) has approved Mayzent® (siponimod) for the treatment of adults with relapsing forms of multiple scl...

Compound that kills drug-resistant fungi is isolat…

Antimicrobial and antifungal resistance, which describe the ability of bacteria and other pathogens to resist the effects of drugs to which they were once sensitive, is a...

First bacterial genome created entirely with a com…

All the genome sequences of organisms known throughout the world are stored in a database belonging to the National Center for Biotechnology Information in the United Sta...

Liver, colon cancer cells thwarted by compounds de…

The plant that adds flavor, color and bitterness to beer also produces a primary compound that thwarts cancer cells, and two important derivatives of the compound do as w...

Clinical trial finds therapy to be well-tolerated …

A phase I clinical trial that set out to assess the safety of a new combination therapy for a type of aggressive brain tumour has found the treatment to be well tolerated...

Immune cells fighting blood cancer visualized for …

When cancer escapes the immune system, our defenses are rendered powerless and are unable to fight against the disease. Chimeric antigen receptor T cells (CAR T cells) re...

FDA approves treatment for patients with a type of…

The U.S. Food and Drug Administration today approved Cimzia (certolizumab pegol) injection for treatment of adults with a certain type of inflammatory arthritis called no...

Boehringer Ingelheim announces FDA and EMA regulat…

Boehringer Ingelheim has filed for regulatory approval of nintedanib in patients with systemic sclerosis associated interstitial lung disease (SSc-ILD) with the FDA and E...

Selumetinib granted US Breakthrough Therapy Design…

AstraZeneca and MSD, Inc., Kenilworth, NJ, US (MSD: known as Merck & Co., Inc. inside the US and Canada) today announced that the US Food and Drug Administration (FDA) ha...

Novartis adds clinical and preclinical anti-inflam…

Novartis announced that it is adding to its broad portfolio of immunomodulatory medicines with the planned acquisition of IFM Tre, a subsidiary of IFM Therapeutics LLC fo...

Forxiga approved in Japan for type-1 diabetes

The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Forxiga (dapagliflozin) as an oral adjunct treatment to insulin for adults with type-1 diabetes (T...

Novartis continues transformation into a leading m…

Novartis today completed the spin-off of the Alcon eye care devices business through a dividend-in-kind distribution to holders of Novartis shares and ADRs (American Depo...