Mitochondrial DNA/nuclear DNA ratio in chemotherapy induced neuropathy
Research type
Research Study
Full title
Examination of the mitochondrial DNA/ nuclear DNA ratios and peripheral neuropathy in patients receiving oxaliplatin for colerectal cancer
IRAS ID
117462
Contact name
William Farquhar-Smith
Contact email
Sponsor organisation
Research and Development Royal Marsden
Duration of Study in the UK
0 years, 11 months, 29 days
Research summary
Chemotherapy induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of chemotherapy, affecting up to 70% of patients after agents such as paclitaxel, oxaliplatin, and bortezomib. CIPN causes several problems including numbness and pain that can significantly affect quality of life. CIPN is a major clinical problem because it can result in the cessation of chemotherapy, is often persistent for months/years and currently lacks effective therapy. Prevention of CIPN would be greatly aided if we could identify those patients likely to develop CIPN and therefore target those patients for prophylactic therapy.
Deoxyribonucleic acid (DNA) carries genetic information and is present in the nucleus of all cells (nuclear DNA (nDNA)). Mitochondria are in all cells and generate energy. Mitochondria contain a similar but separate DNA to nDNA, known as mitochondrial DNA (mtDNA). Mitochondrial dysfunction in nerves plays a role in the generation of CIPN. Moreover, recent data in rats has shown significant changes in mtDNA/nDNA ratio levels in the blood that correlated to the emergence of chemotherapy-induced pain behaviours suggesting that mtDNA/nDNA levels could be a biomarker for CIPN. This pilot study will assess changes in mtDNA/nDNA ratio in the blood in patients with CIPN caused by oxaliplatin in patients with colorectal cancer. Oxaliplatin is responsible for many patients with CIPN at RMH.
Hypothesis: Chemotherapy (oxaliplatin)-induced neuropathy causes a change in blood mtDNA/nDNA ratio correlating with the development or worsening of CIPN and/or painful CIPN. The study will also examine mtDNA/nDNA ratio before oxaliplatin treatment and examine if this is a risk factor for neuropathy. This investigation is the first 'proof of concept' stage that could potentially lead to the development of a simple screening test to identify patients at high risk of neuropathy following chemotherapy.REC name
London - Riverside Research Ethics Committee
REC reference
15/LO/0174
Date of REC Opinion
16 Feb 2015
REC opinion
Favourable Opinion