Rectal cancer is one of the most common cancers worldwide. Neoadjuvant chemoradiation therapy (CRT) prior to surgery is fast becoming the standard of care. Patients who achieve a complete pathological response(pCR) following neoadjuvant CRT have reduced local recurrence, reduced distant metastases and improved survival. However, tumour resistance to neoadjuvant CRT is a substantial clinical problem, with only ~15-27% of patients achieving a pCR.
This innovative project supports the strategy of the HRB and Trinity College Dublin toaddress an unmet global healthcare challengein rectal cancer. We will develop a novel treatment strategy: targeting MEtabolism for individualised Rectal cancer Treatment (MERiT), by identifying prior to treatment, those patients who will derive a benefit from neoadjuvant CRT, and developing a novel therapeutic strategy to improve the response to neoadjuvant CRT in those patients who are resistant to the current standard of care.
This novel project will build on our expertise and will bring together a multinational, multidisciplinary team of scientists, healthcare professionals, surgeons and pathologists to determine the role of altered energy metabolism in the resistance of rectal cancer to CRT. This innovative project will utilise pre-treatment tumour tissue, blood and novel tumour explant models from rectal cancer patients attending St James’ Hospital Dublin, a national cancer centre of excellence, and novel in vitro models of radioresistance. We will integrate metabolomic and transcriptomic networks to identify a novel predictive signature of CRT response and will validate a patented, novel small molecule drug as a novel anti-metabolic radiosensitiser in rectal cancer, to improve patient stratification and treatment. This will impact on clinical practice, aiding clinicians in treatment stratification and planning, and enabling individualised treatment, which will improve patient treatment and survival, leading to real and tangible impact on the lives of patients and families both in Ireland and worldwide.
