A novel high-throughput approach to stratify patients based on chemotherapeutic response

Cancer is a devastating disease and is more prevalent in Wales than other countries of the UK (CR-UK figures).

The mainstay cancer treatment, chemotherapy is effective in only some patients. Indeed, some patients undergoing chemotherapy find that their cancer actually spreads. This form of resistance to therapy is complex and is governed by a myriad of genetic interactions that are unique to each tumour/patient.

At present it is not feasible (due to high costs) to dissect these detailed genetic factors and plan tailored therapy for all patients. However, we urgently need to better understand the effectiveness of chemotherapy early enough so that patients and clinicians can make informed decisions about whether to switch treatment regimens (if it is not working) or in some cases to cease treatment if there is no benefit.

Until now, the mixed response to chemotherapy in different patients has only been apparent after the treatment ends and once scans show either shrinkage of the tumour, or no change in tumour size.

We have developed a 'low-cost' blood test that sensitively measures circulating DNA mutations in blood cells induced by chemotherapy. We have trialled this in oesophageal cancer patients and have shown some patient's blood cells respond to the chemotherapy and many mutations are induced, however others show minimal response with very few mutations induced.

This test may then act as a surrogate for the 'response' of the tumour to therapy and may identify the responders and the non-responders to chemotherapy - actually during the treatment phase.

Hence, it may be possible to intervene early using this technology in cases where patients are not responding and switch treatments between cycles. This studentship will create further pilot data, building on the preliminary investigations carried out to date and provide evidence as to whether this approach can be clinically useful.