hydroxychloroquine MDT

Additional highlights included the differential roles of bulk autophagy versus selective autophagy, novel autophagy regulators, and emerging chemical tools to study autophagy inhibition. Interdisciplinary discussions focused on addressing questions such as which stage of disease to target, which type of autophagy to target and which component to target for autophagy modulation.

It was found that the levels of basic autophagy in multidrug‑resistant leukaemia cells (K562/ADM) were significantly higher compared with sensitive cells (K562), and that Adriamycin (ADM) was capable of inducing autophagic activity in K562 and K562/ADM cells. Collectively, these findings indicated that the inhibition of autophagy significantly promoted the sensitivity of K562/ADM cells to ADM by facilitating apoptosis. Furthermore, inhibition of autophagy attenuated the expression of P‑gp; therefore, P‑gp may be involved in autophagic regulation in drug‑resistant cells.

Therapy-induced autophagy is a major resistance mechanism to targeted therapy, and chloroquine (CQ) derivatives, which inhibit lysosomal palmitoyl-protein thioesterase 1 (PPT1), augment the efficacy of BRAF and MEK inhibitors in preclinical models. Here, we report that the CQ derivative, hydroxychloroquine (HCQ) enhanced the efficacy of anti-PD-1 Ab and the survival of immunocompetent mice bearing B16 mouse melanoma tumors...Together, this data indicates that in addition to direct antitumor cell activity, CQ derivatives elicit immunomodulatory properties that enhance tumor immunity when combined with anti-PD-1 Ab treatment. This therapeutic approach will be tested in the clinic which will start accruing patients by 2020.