Solving the problem of treatment resistance

Dr Holly Barker studied the effect of inhibiting an enzyme involved in DNA replication and repair (CHK1 inhibitor) in ‘sensitizing’ and thereby improving response to radiotherapy.

Results showed that combining radiation, chemotherapy and a CHK1 inhibitor not only showed benefit in reducing tumour growth but also meant that the dose of chemotherapy could be reduced, meaning potential to reduce toxicity.

As well as defining the best treatment schedule of this triple combination, Dr. Barker also went on to study patient samples to identify which tumours are likely to recur after radiotherapy and how this resistance could be overcome. By looking at CHK1 expression in patient tumour samples it was found that this enzyme is more active in tumours that recur after radiotherapy. Therefore CHK1 could be used as a marker to identify tumours that are likely to recur and thus patients who are likely to benefit the most from adding a CHK1 inhibitor alongside chemotherapy during radiotherapy i.e. the triple combination.

Kevin Harrington at the ICR, said, “Radiotherapy is the standard-of-care treatment for patients with many different types of cancer. However, tumors of the same size and stage can respond very differently to radiation, and new approaches to overcoming radioresistance are badly needed. Combinations of treatments are used routinely to treat infectious disease to combat antimicrobial resistance. So it makes sense that we would employ the same strategy for cancer.”

“Our research has shown that a triple combination of a CHK1 inhibitor, paclitaxel chemotherapy, and radiotherapy holds great promise for treating head and neck cancers, but also for overcoming therapy resistance and hopefully preventing relapse. We are now planning to take this course of treatment into the clinic to trial in patients.”

This project was funded from Oracle’s unrestricted reserves.