Doxycycline Restores Gemcitabine Sensitivity in Preclinical Models of Multidrug-Resistant Intrahepatic Cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a rare but aggressive liver cancer with limited treatment options, especially when tumors become resistant to standard drugs like gemcitabine. This study investigates whether doxycycline, an antibiotic, can restore the effectiveness of gemcitabine in treating drug-resistant iCCA. Using in vitro models, we found that doxycycline reduces the survival and stem-like properties of cancer cells. In mouse models, the combination of doxycycline and gemcitabine significantly shrank tumors that were otherwise resistant to treatment. These findings suggest that doxycycline could be repurposed to improve outcomes for patients with this challenging cancer, offering a potential new combination therapy for clinical use.