For most patients with metastatic colorectal cancer, a combination of chemotherapy and targeted monoclonal antibody constitutes the standard of care treatment. However, a significant fraction of patients does not exhibit tumor response or at least stabilization due to primary resistance. Further, in case of initial tumor response or stabilization, nearly all patients develop a resistant disease during the further course of treatment, named as secondary resistance. Most of these patients finally succumb to the progressive metastatic disease. Hence, there is an urgent medical need to better understand the primary and secondary resistance against systemic treatment in patients with metastatic colorectal cancer.

This is exactly where REVEAL steps in. This project is coordinated at the DKTK partner sites in Munich and Berlin. With the analysis of genetic information as well as gene expression profiles of colorectal cancer specimens, the researchers aim at identifying molecular causes for resistance against treatment. Further, the prospective, multicenter REVEAL study evaluates tumor specimens derived from liver metastases, which are collected during standard first-line systemic treatment. This approach is complemented by the analysis of blood samples, in which the tumor-associated genetic alterations can be easily tracked during the course of treatment (liquid biopsy).

The aim of REVEAL is to unravel molecular mechanisms of primary and secondary resistance against systemic treatment in metastatic colorectal cancer. With this knowledge, oncologists might better anticipate the individual benefit patients derive from specific antineoplastic drugs. Once validated in further clinical trials, this might help to optimize patient management and ameliorate the limited prognosis of patients with metastatic colorectal cancer.

Between 2014 and 2018, REVEAL recruited successfully at six German cancer centers a total of 70 patients. With an adequate follow-up time and completion of the molecular analyses in late 2020, first results of REVEAL are foreseen in 2021.