Translating preclinical research into effective treatment protocols for individuals with cancer is a complex and challenging task. One major obstacle is the highly variable genetic makeup of tumor cells, as well as the impact of the tumor microenvironment on drug response. In order to find new clinically relevant drug combinations for colorectal cancer (CRC), researchers have turned to ex vivo platforms to test potential combinations on fresh human tumor samples.
In this study, we aimed to identify the most promising drug combinations for CRC by first performing a large in vitro screen, where hundreds of different combinations were tested for synergistic effects. From this screen, the top five combinations were selected for further testing on 29 freshly resected human CRC tumors using an ex vivo platform. The results of this study showed that the combination of MEK and Src inhibition was the only combination that was effective when tested on fresh human tumor samples.
Furthermore, the study identified a potential biomarker for predicting response to this drug combination, phosphorylated Src (pSrc), which was found to be predictive in cases where the tumor did not carry KRASG12 mutations. This demonstrate the potential of ex vivo platforms to identify effective drug combinations and to uncover new clinically relevant drug combinations in a predefined subset of individuals with CRC. This approach could be used to help guide future clinical trials and improve outcomes for patients with cancer.