Transcriptomic signature reveals sensitivity to tubulin inhibitors in colon cancer

Colon cancer is the second most common cause of cancer death worldwide. Despite advances in the development of new molecular strategies for stratifying patients with colon cancer, many of these patients do not respond adequately to the standard of care. While previous studies have focused on the development of prognostic gene expression signatures, the exploration of predictive signatures to inform treatment decisions remains incomplete. In this study, we leveraged public gene expression datasets to design and experimentally validate a 37-gene expression signature for prognosis in colon cancer patients. We obtained a C-index of 0.732 (0.610-0.853) in four independent studies. Specifically, we discovered that the signature is associated with the mitotic phase of the cell cycle. Furthermore, the signature identified a population of colon cancer patients sensitive to tubulin inhibitor drugs. In particular, we validated in vitro and in vivo the efficacy of paclitaxel, a commonly used tubulin inhibitor in breast cancer treatment, in patient-derived preclinical models. These results highlight the importance of incorporating gene expression signatures to identify new therapeutic options for colon cancer treatment. Furthermore, the identification of alternative treatment options with potentially improved efficacy holds promise for the development of new clinical trials, and reshapes the biomarker-based treatment strategy for second line and refractory colon cancer patients.