Colorectal cancer is the third cancer incidence rate and fifth mortality rate in China. In 2018, there were about 521490 new cases and 247563 deaths in China. In recent years, although the mortality rate of intestinal cancer has dropped slightly, the incidence rate has shown a younger trend.
The literature shows that about 20% - 25% of the newly diagnosed colorectal cancer patients have metastases at the time of treatment. Although first-line chemotherapy based on irinotecan or oxaliplatin combined with epidermal growth factor receptor (EGFR) targeted drug treatment for metastatic colorectal cancer can increase the median overall survival time (MOS) by more than 2 years. However, about 30% - 50% of CRC patients have no response to EGFR inhibitor treatment, because they have mutations in exon 2 of KRAS gene, which is a predictable biomarker of EGFR inhibitor resistance. The choice of other new targeted therapies for these patients is also limited.
The research team of Zhongshan Hospital, from epidemiology to molecular mechanism, deeply analyzed the anticancer effect of metformin. Through the retrospective analysis of the medical records of more than 2000 colorectal cancer patients, and the in vitro and in vivo experiments, the research team basically clarified the mechanism of metformin's anticancer effect on the metastatic colorectal cancer carrying KRAS mutation. It was through KRAS mutation that the level of membrane channel protein mate1 decreased, which made metformin accumulate in the cancer cells and achieve inhibition after reaching a certain concentration The role of cancer cell proliferation.
At present, the team is planning to start prospective research, which is worth looking forward to!