Problem addressed, background and strategic significance

Colorectal cancer is the second most common cancer in developed countries and rectal cancer constitutes approximately one third of all colorectal cancers. Patients with rectal cancer require major surgery to remove the cancer and in some cases this will involve a permanent stoma. Some patients with rectal cancer require treatment with radiotherapy and chemotherapy prior to surgery and respond so well that the cancer may appear to be cured, whilst others do not respond at all. At present it is impossible to predict which patients will have a complete response to chemoradiotherapy, and therefore may not require surgery. Mitochondria are the powerhouses of the cells which depend on oxygen to produce energy. Rectal cancer cells sometimes have genetic alterations causing the mitochondria to not function properly. When this happens the cells adapt to produce energy in the absence of oxygen which may make them resistant to the damaging effects of chemoradiotherapy as this treatment relies on a good oxygen supply to kill the cells. We aim to investigate whether we can use mitochondrial genetic alterations to predict response to chemoradiotherapy.

Method(s) used

We will investigate mitochondrial function and genetic alterations in biopsies from patients undergoing chemoradiotherapy for rectal cancer by sequencing the mitochondrial DNA and looking at mitochondrial protein levels. We will then compare results from patients with varying responses to chemoradiotherapy.

Hoped for results of this research

We hope that it may be possible from this study to identify mitochondrial genetic markers which could predict how patients will respond to chemoradiotherapy and allow us to tailor their treatment accordingly.

How will this project help build on the Delphi question and what further plans are proposed for future development?

Mutations in the mitochondrial DNA may help to predict which patients will have a complete response to chemoradiotherapy and therefore could potentially avoid surgery and undergo surveillance instead of surgery. If the results from this pilot study are promising, we will perform a multi-centre study with a large number of patients to try to answer this question.