New Class of Drugs Could Halt Ovarian Cancer Cell Growth

PARG Inhibitor Exploits Weakness, Kills Cells

Researchers from the UK’s University of Manchester have shown that a new class of drugs are able to stop ovarian cancer cells growing.

A study published in Cancer Cell showed that the drugs, known as PARG inhibitors, can kill ovarian cancer cells by targeting the cells’ ability to copy their DNA.

PDD00017273, a first-in-class PARG inhibitor, was discovered in the Drug Discovery Unit at the Cancer Research UK Manchester Institute as part of a targeted program to discover PARG inhibitors for the clinic. 

The findings are promising for patients with ovarian cancer, the sixth most common cause of cancer in women in the UK. In the U.S., ovarian cancer is the fifth leading cause of cancer among women, and some 22,530 women are expected to receive a new diagnosis of ovarian cancer in 2019.

Scientists were able to screen ovarian cancer cells for specific genes that, when knocked out, would initiate PARG-inhibitor sensitivity. The researchers identified the key genes that made cancer cells sensitive to PDD00017273, which were those involved in DNA replication.

In addition, the team demonstrated that the PARG inhibitor can also be used in combination with other clinically accessible drugs, such as CHK1 and WEE1 inhibitors, to kill ovarian cancer cells taken directly from samples from patients treated at the Christie Hospital in Manchester. The researchers hope that their work will provide further impetus for developing a PARG inhibitor for use in human trials.

Source: EurekAlert!, March 19, 2019