Development of personalised medicine approaches for the clinical application of IAP antagonists in metastatic and high risk early stage colorectal cancer

Colorectal cancer (CRC) has the second highest mortality rate of any cancer in Europe. Globally, there are 1.2 million cases diagnosed each year. For current therapies, the weekly cost per patient can reach €5,000, but benefits to patients are limited. 5-year survival rates have increased only moderately in the past 25 years, indicating a need for novel therapies that target cancer resistance. However, devising new therapies but not knowing which patients will ultimately benefit from these is unsustainably costly. Based on novel diagnostic tools and a substantial body of biomedical, pre-clinical and clinical data generated by the applicant group, this proposal explores the hypothesis that subgroup(s) of colorectal tumours become addicted to inhibitor-of-apoptosis (IAP) proteins, thereby suppressing both apoptosis and immune signalling, and that such subgroup(s) can be effectively treated by novel IAP-targeted therapeutic drugs. We will identify sub-groups of patients not benefiting from current chemotherapy, examine which subgroup(s) of tumours are re-sensitized by IAP antagonist therapy, and will deliver a new generation of systems-based patient stratification tools for future integration into ‘smart’ clinical trials. Our proposal will deliver new solutions for the personalised therapy of CRC, and addresses these in a systematic, step-wise manner.

Project ends 2017 Funded by SFI

SFI - Science Foundation Ireland