Can mtDNA mutations predict chemoradiotherapy response in rectal cance
Research type
Research Study
Full title
Investigating the use of mitochondrial DNA mutations as predictors of response to pre-operative chemoradiotherapy in rectal cancer
IRAS ID
228668
Contact name
Laura Greaves
Contact email
Sponsor organisation
Northumbria Healthcare NHS Foundation Trust
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
Colorectal cancer (CRC) is the second most common cancer in developed countries. Rectal cancer constitutes approximately one third of all CRCs. 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 chemoradiotherapy (CRT) 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 CRT, 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 radiotherapy 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 CRT.
We will investigate mitochondrial function and genetic alterations in pre-treatment biopsies from patients who have subsequently had CRT for rectal cancer. We will then compare results from patients with varying responses to CRT.
We hope that it may be possible from this study to identify mitochondrial genetic markers which could predict how patients will respond to CRT and allow us to tailor their treatment accordingly.
Mutations in the mitochondrial DNA may help to predict which patients will have a complete response to CRT 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.
REC name
HSC REC A
REC reference
19/NI/0010
Date of REC Opinion
15 Jan 2019
REC opinion
Favourable Opinion