A systems-based patient stratification tool of Bcl-2 family protein interactions to evaluate acute treatment responses in rectal cancer patients

Cancers of the rectum (the lower part of the large intestine where the body stores stool) are a common cause of cancer-related death in Ireland and cause a significant burden to the quality of life of affected patients. Surgery is the mainstay for the treatment of rectal cancer, but surgeons often prefer to 'downstage' or 'shrink' the tumour prior to surgery in order to achieve a better surgical outcome and to reduce surgical complications or the necessity of a stoma. This 'downstaging' of the tumour is achieved through aggressive radio- and chemotherapy over a period of two - three months, however many patients will not respond to this treatment because their cancer cells are resistant to such therapy. Hence for a majority of patients the radiochemotherapy may not only be unnecessary, but may even delay surgery and increase the risk of further tumour progression. In a previous, successful study in colon and rectal cancer patients [1], we developed a new test that is capable of telling the surgical and medical teams whether a patient will respond or not to radiochemotherapy by analysing a set of proteins from a small biopsy of the tumour that is routinely taken during medical examination. Rather than looking at individual proteins or genes, this diagnostic test takes into account the complex regulation of tumour cell death in response to radiochemotherapy. Here we will validate this new diagnostic tool in a larger cohort of rectal cancer patients, and will further improve it by investigating whether the inclusion of important genetic and other patient data increases its predictive power. Finally, we will investigate whether this new diagnostic tool can also be used to identify those patients who may benefit from novel therapeutics that target cell death defects and that are currently in the clinical testing phase.

Award Date: 19 June 2014
Award Value: €313,839
Principal Investigator: Professor Jochen Prehn
Host Institution: Royal College of Surgeons in Ireland
Scheme: Health Research Awards