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New Drug (CHK1 Inhibitor) Could Enhance Chemotherapy Effects, First Clinical Trials Scheduled in Lung and Pancreatic Cancer Patients

A new drug that blocks cancer's escape route from chemotherapy could be used to treat deadly lung and pancreatic cancers, new research reports. Scientists have shown in human cancer cells and in mice that the drug, which was discovered at The Institute of Cancer Research in 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. CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The new study was published online on July 22, 2015 the journal Oncotarget, and was funded by Cancer Research UK and Sareum Limited. The article is titled “The Clinical Development Candidate CCT245737 Is an Orally Active CHK1 Inhibitor with Preclinical Activity in RAS Mutant NSCLC and Eµ-MYC Driven B-cell Lymphoma.” The research, conducted at The Institute of Cancer Research (ICR) in collaboration with colleagues at the drug discovery company Sareum and at 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 that 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 also 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.

It is possible that CHK1 inhibitors such as CCT245737 - which was designed and synthesised at the ICR with funding from Cancer Research UK - could be used on their own to treat other types of cancer with similar levels of DNA damage.

The intellectual property associated with the project was licensed to the CRT Pioneer Fund (CPF) which is now working with Sareum, to take the project into Phase I clinical trial before commercialization.

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 tumors 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."

Dr. Tim Mitchell, CEO of Sareum Limited, said: "The publication of CCT245737 data in this high-impact journal will bring what we believe to be a best-in-class drug candidate to the attention of our peers and potential licence partners. The preclinical studies are progressing well and we look forward to providing an update with our final results."

Dr. Phil L'Huillier, Cancer Research Technology's Director of Business Development, said: "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."

[Press release] [Oncotarget abstract]