Tumor cells evade death and become chemo-resistant through autophagy: Study by Craig B. Thompson MD and colleagues to appear in February issue of the Journal of Clinical Investigations

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Abramson Cancer Center News of the University of Pennsylvania
Last Modified: January 19, 2007

Autophagy is a cellular process that enables cells to digest their contents. Autophagy is initiated in tumor cells by chemotherapy and radiation. It is not known how this process may contribute to tumor cell death or helps tumor cells become resistant to cancer treatments. In a study using a mouse model of B cell lymphomas, investigators from the Abramson Cancer Center of the University of Pennsylvania and the Abramson Family Research Institute, the basic science branch of Penn's Cancer Center, have now shown that autophagy is a mechanism for tumor cells treated with agents to escape chemotherapeutic induced 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 B. Thompson MD, Director of the Abramson Cancer Center, Andrei Thomas-Tikhonenko, Abramson Cancer Center member, and colleagues show that in tumor cells in which apoptosis was induced by activation of p53 expression with chemotherapy, autophagy was observed only in tumor cells not undergoing cell death, suggesting a mechanism for tumor cell survival and resistance to chemotherapy. If, however, mice were given inhibitors of autophagy in addition to 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.

To read the on-line article: Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma