Repurposing DPP-4 Inhibitors for Colorectal Cancer: A Retrospective and Single Center Study

SIMPLE SUMMARY: Colorectal cancer is one of the most common causes and the leading cause of cancer deaths worldwide. Its poor prognosis highlights the urgent need for more effective treatments. Repurposing approved drugs is a promising strategy as preclinical screenings can be minimized. The aim of our retrospective study was to investigate the potential of Dipeptidyl-peptidase 4 (DPP4)-inhibitors, which are safe Food and Drug Association (FDA)-approved drugs for treating diabetes, in treating CRC patients. Our findings conclude that CRC patients with diabetes and treated with DPP4-inhibitors in our hospital during 2006–2015, their 5-year prognosis following curative resection was significantly better than those treated with metformin. We further showed that their prognosis was associated with immune cell population features that associated with better prognosis, and immune cell profile is a biomarker for predicting the prognosis of DPP4-inhibitors treated CRC patients. ABSTRACT: Background: There have been studies reporting the crucial roles of Dipeptidyl-peptidase 4 (DPP4) in colorectal cancer (CRC) initiation and progression, whereas DPP4-inhibitors are safe Food and Drug Association (FDA)-approved drugs for treating diabetes. This study aims to investigate the association between DPP4-inhibitor treatment and the prognosis of CRC patients. Methods: Clinical data of CRC patients with diabetes and the prescription of DPP4-inhibitors who had undergone curative surgery in our hospital between January 2006 and December 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared to those treated with metformin. Results: The DPP4-inhibitor patient group showed a significantly better 5-year disease-free survival (median DFS = 1733 days, 95% CI = 1596 to 1870 days) when compared to the metformin group (p = 0.030, median DFS = 1382 days, 95% CI = 1246 to 1518 days). 33 out of the 92 patients in the metformin group showed recurrence whereas only 3 of the 26 patients in the DPP4-inhibitor group showed recurrence (p = 0.033). Cox regression analysis demonstrated that DPP4-inhibitor application is a favorable factor associated with a lower risk of recurrence (Hazard ratio = 0.200, p = 0.035). Furthermore, our results suggested that the immune cell profile of CRC patients is a potential biomarker for response to DPP4-inhibitor treatment. Conclusion: This study demonstrated the association of DPP4-inhibitor treatment with a better prognosis of CRC patients.