CancerA new drug that blocks cancer’s escape route from chemotherapy could be used to treat deadly lung and pancreatic cancers, according to new research.

Scientists have shown in human cancer cells and in mice that the drug – discovered at The Institute of Cancer Research, London – boosts the effectiveness of conventional chemotherapy.

The drug, known as CCT245737, is scheduled to begin first-in-human clinical trials in patients with lung and pancreatic cancers – two cancers with low survival rates that continue to resist currently available treatments.

Professor Ian Collins, Professor of Medicinal Chemistry at The Institute of Cancer Research, London, said: "We’re excited that our new CHK1 inhibitor, which was discovered at the ICR in collaboration with Cancer Research UK and Sareum, is progressing towards first-in-human clinical trials.

"By using CHK1 inhibitors with chemotherapy, we block one of cancer’s escape routes and prevent tumours from evading the effects of treatment. We hope that clinical trials of our new drug will show it to be an effective chemotherapy booster in lung and pancreatic cancers, which readily become resistant to current treatments."

The research, conducted at the Institute of Cancer Research (ICR) in collaboration with colleagues at the drug discovery company Sareum and Newcastle University, shows the effectiveness of a new class of drugs called CHK1 inhibitors that can be delivered orally to patients.

Most chemotherapies work by damaging the DNA of rapidly dividing cells. But in response, cancer cells activate a molecule called CHK1 which delays cell division and gives cancer cells time to repair their damaged DNA. Scientists hoped that blocking CHK1 could stop cancer cells from repairing DNA damage and prevent them from becoming resistant to the cell-killing effects of chemotherapy.

Researchers developed techniques to assess the method of action of CCT245737 in human cancer cell lines, and demonstrated that it potently blocked the molecule CHK1. They also assessed CCT245737 in combination with chemotherapy in mice with tumours grown from human cancer cell lines, and found it achieved much greater anti-cancer activity than chemotherapy alone. Importantly, the mice did not experience any additional toxicity of the combined drugs.

Researchers found that the CHK1 inhibitor could be used alone, without additional chemotherapy, to treat a type of blood cancer called lymphoma because this cancer type sustains heavy DNA damage during its formation.

Dr Phil L’Huillier, Cancer Research Technology's director of business development, added: "The CRT Pioneer Fund was set up to help bridge the funding gap between the lab and the clinic and we’re delighted that this investment from CPF and Sareum means a promising molecule is now ready for clinical trials. Lung and pancreatic cancers have some of the lowest survival rates of any cancer type, so we hope this vital injection of cash and resources will mean patients can benefit from this research sooner."

To read the study findings in full visit http://www.icr.ac.uk