New drug type could boost chemotherapy

Scientists at The Institute of Cancer Research, in conjunction with cancer drug discovery company Sareum, have shown that a new type of drug could boost the effectiveness of chemotherapy treatments for many cancer types.

The oral compound they discovered blocks a molecule called Chk1, which cancer cells rely on more heavily than normal cells to repair damage to their DNA.

The ICR scientists hope that blocking Chk1 will reduce cancer cells’ ability to fix the damage caused by chemotherapy drugs given at the same time, while normal cells will be able to use other mechanisms to repair themselves and remain largely unscathed.

In lab studies, the scientists showed that more cancer cells died when the Chk1 inhibitor, called CCT244747, was given 24 or 48 hours after the chemotherapy agents gemcitabine or irinotecan than when these drugs were given alone.

The drug was tested on colon, pancreatic and non-small cell lung cancer cells with a common cancer-linked mutation called p53. It also killed neuroblastoma cells with a MYCN mutation when given alone.

The study, published in Clinical Cancer Research, represents the first time details have been published of an orally bioavailable Chk1 inhibitor that has killed cancer cells in the lab.

“We found that the addition of our Chk1 inhibitor significantly boosted the tumour cell-killing properties of two chemotherapy drugs,” said Dr Michelle Garrett, a team leader in the Cancer Research UK Cancer Therapeutics Unit at The Institute of Cancer Research (ICR). “This is the first published demonstration of the promise of these type of compounds. Our team is collaboratively investigating several Chk1-inhibiting drugs and we look forward to progressing the best of these towards the clinic, both in combination with chemotherapy and as a single drug.”

The ICR has a collaboration with Sareum and CRT to discover and develop Chk1-inhibiting drugs. Another Chk1-inhibiting candidate drug from their joint research collaboration has been selected to progress towards clinical trial.