A translational systems biological study to identify molecular predictors for responsiveness to TRAIL-receptor agonists in colorectal cancer

Many patients that suffer from cancer of the colon require chemotherapy. Chemotherapy is supposed to induce the death of cancer cells by a molecularly controlled death process called apoptosis. Apoptosis in response to chemotherapy requires the activation of cell death genes, but colon cancer cells often can prevent these genes from being activated, resulting in the failure of chemotherapy. Novel therapeutics such as 2nd generation activators of "death receptors" on the surface of cancer cells provide us with the possibility to trigger apoptosis without the requirement for gene activation. These novel drugs have been tested with great success in initial studies but are not yet available to patients. To optimally design clinical studies in which patients are offered these drugs alone or in combination with chemotherapy, tools are required which can predict for individual patients whether they are likely to respond to treatment.
Here, we will develop such tools by an interdisciplinary approach that integrates the latest and most relevant colon cancer research methodologies and superior mathematical data analysis procedures to generate reliable predictions on treatment responsiveness. Our study builds on a substantial amount of promising preliminary data and will set an example for how innovative research strategies can address significant clinical needs. Assessing novel treatment options and providing these in an optimised and personalised manner can benefit large numbers of colon cancer patients in the future.

Award Date
23 October 2015
Award Value
Principal Investigator
Dr Markus Rehm
Host Institution
Royal College of Surgeons in Ireland
Health Research Awards