Colorectal cancer (CRC) is the most common gastrointestinal malignancy. There are approximately 664,000 new cases each year worldwide. Half of these patients will die from this carcinoma. Currently, standard treatment is primary surgery and depending on the tumour stage, additional chemotherapy. Due to the high recurrence rate, new potential targets and prognostic markers are needed to identify patients that are likely to benefit from additional therapy.
On molecular levels ‘‘The Cancer Genome Atlas Network’’ demonstrated that deregulated c-Myc expression is a hallmark of virtually all CRCs, independent of the set of specific mutations that are present in each tumour. For example, mutations in the tumour suppressor APC and the oncogene KRAS lead to an up regulation of MYC mRNA. On posttranscriptional level, the loss of miR34 family by hyper methylation, which occurs in over 90% of all CRC, stabilizes MYC mRNA. Furthermore, a mouse model of colon cancer driven by loss of APC shows that colon tumour formation depends on continuous c-Myc expression.
Overall c-Myc is an interesting target for treating CRC. Unfortunately so fare there are no sufficient inhibitors that could be used in vivo.
Our main research interests are therefore is on two major points that regulate c-Myc in CRC:
A) to define components that are in a synthetic lethal relationship to mutation or loss of the tumor suppressor APC.
B) Dissect the posttranscriptional regulation of c-Myc in CRC.