부산대학교 도서관

Summary: Currently, the only autophagy inhibitor available clinically is CQ or derivative hydroxycholorquine (HCQ). It is still uncertain whether these drugs can actually achieve autophagy inhibition in patients. Dogs serve as a good model for human cancer and there is an unmet need for novel therapies in the treatment of canine lymphoma. Thus we conducted a phase I clinical trial in canine lymphoma patients with the goals of finding a maximum tolerated dose in combination with doxorubicin (DOX) and the relationship of HCQ concentration and autophagy inhibition. We found that this combination can be well tolerated with a 20% reduction in DOX. HCQ can achieve autophagy inhibition in patients, but not consistently. There appears to be a threshold requirement of HCQ needed in order to effectively inhibit autophagy. There was a suggestion of efficacy as response rate was superior to historical data employing DOX alone. Therefore autophagy inhibition warrants further clinical study as an anti-cancer therapy.