Mol cancer therapy: scientists are expected to develop a new targeted therapy for malignant progressive cholangiocarcinoma

January 19, 2020 / BIOON / -- recently, an international magazine published in molecular cancer therapeutics In the previous study, scientists from Ohio State University Medical Center revealed how patients with cholangiocarcinoma can tolerate potential targeted drugs; adding another drug called FGFR inhibitor to cancer progression may effectively make cancer cells sensitive to the first drugs Photo source: sameek Roychowdhury, MD, Ohio State University Medical Center In this study, most of the patients with FGFR positive cholangiocarcinoma will benefit from the treatment of new FGFR inhibitors, however, many of them are unfortunately resistant to drugs In this study, researchers have a deep understanding of the mechanism of drug resistance in patients with cholangiocarcinoma, which is very important for the later development of new therapies to treat cancer caused by abnormal FGFR gene mutations The results show that monitoring the circulating tumor DNA fragments that promote the resistance of FGFR inhibitors and are prone to acquired mutations may reveal the existence of drug-resistant mutations and mark the time when patients begin to take mTOR inhibitors Successful treatment of cholangiocarcinoma is challenging because it is often diagnosed only in the advanced stage, and the 5-year survival rate of patients is only 2% Because of the high recurrence rate, even the 5-year survival rate of patients diagnosed in the early stage is very low Abnormal activation of FGFR occurs in about 15% - 20% of patients with cholangiocarcinoma, and FGFR inhibitors can effectively treat 70% - 80% of patients until drug resistance occurs At present, there are six studies on FGFR inhibitors in clinical; researcher Melanie Dr Krook said that in-depth understanding of the mechanism of cancer resistance to therapy and how to effectively prevent or help develop new therapies for cholangiocarcinoma and other cancers caused by FGFR mutations The results show that FGFR targeted therapy for cholangiocarcinoma patients may benefit from combination therapy of other drugs, such as mTOR inhibitors Later researchers need to conduct in-depth research to identify the best combination therapy In this study, the researchers analyzed the expression of FGFR (fibroblast growth factor receptor) gene in human cholangiocarcinoma cells These patients experienced disease progression and died after they were resistant to FGFR inhibitor infinib Finally, the researchers said that they were in patients with tumors Two kinds of acquired FGFR mutations which can mediate the drug resistance of FGFR inhibitors were identified in the cells Then the researchers used cancer cell lines to study how these mutations activate the mTOR signal pathway, which can make cancer cells survive in the presence of FGFR inhibitors Adding mTOR inhibitors to the cell culture medium can restore the sensitive state of cancer cells to FGFR inhibitors 。 Original sources: Melanie a Krook, Alexandria lenyo, Max Wilberding, et al Efficiency of FGFR investors and combination therapies for acquired resistance in FGFR2 fusion chocolate, molecular cancer therapeutics (2020) Doi: 10.1158/1535-7163.mct-19-0631