Hyperthermia Reduces Gemcitabine Resistance

Get Permission

Removal of incorporated gemcitabine by DNA repair mechanisms may contribute to resistance to the agent in solid tumors. In a study reported in Journal of the National Cancer Institute, Raoof and colleagues found that radiofrequency-induced hyperthermia blocked repair of gemcitabine-stalled replication forks and thus improved gemcitabine antitumor activity.

The study showed that Mre11-mediated homologous recombination repair of gemcitabine-stalled replication forks was crucial to hepatocellular carcinoma cell survival. Mre11 was inhibited by an exonuclease inhibitor and by radiofrequency field-induced hyperthermia. In orthotopic mouse models of chemoresistant hepatocellular carcinoma, Hep3B tumor mass was significantly smaller with radiofrequency-induced hyperthermia plus gemcitabine vs gemcitabine alone (mean = 180 vs 661 mg, P = .0063).

The investigators concluded: “This study provides mechanistic understanding of homologous recombination inhibiting-strategies, such as noninvasive radiofrequency field-induced hyperthermia, to overcome resistance to gemcitabine in refractory human solid tumors.” ■

Raoof M, et al: J Natl Cancer Inst 106(8):dju183 2014.




By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.