Tumor Cells Evade Death Through Autophagy

Autophagy is a cellular process that enables cells to turnover their contents, something that they do frequently. Autophagy is initiated in tumor cells by chemotherapy and radiation, but it is not known if this contributes to tumor cell death or helps tumor cells survive the anti-cancer therapy. However, in a study using a mouse model of B cell lymphomas, researchers from the University of Pennsylvania have now shown that autophagy represents a survival mechanism for tumor cells treated with agents that initiate tumor cell death by a process known as apoptosis.

In the study, which appears online on January 18 in advance of publication in the February print issue of the Journal of Clinical Investigation, Craig Thompson and colleagues show that in a tumor in which apoptosis was induced by activation of p53 expression, autophagy was observed only in tumor cells not undergoing apoptosis. If mice were unable to initiate autophagy, increased numbers of tumor cells undergoing apoptosis were detected. Furthermore, if these mice were treated with the chemotherapeutic agent cyclophosphamide, tumor cell apoptosis and tumor regression was increased and tumor recurrence was substantially delayed. This study has clinical implications as it indicates that adjunct treatment with inhibitors of autophagy might increase the efficacy of apoptosis-inducing chemotherapeutics in human patients with cancer.

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TITLE: Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma

AUTHOR CONTACT:

Craig B. Thompson
University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Contact: Karen Honey
Journal of Clinical Investigation