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Anti-Apoptosis Mechanisms in Malignant Gliomas

David S. Ziegler, Andrew L. Kung, Mark W. Kieran

From the Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital; and Harvard Medical School, Boston, MA

Corresponding author: David S. Ziegler, MBBS, FRACP, Center for Children's Cancer and Blood Disorders, Sydney Children's Hospital, High St, Randwick, NSW, 2031, Australia; e-mail: d.ziegler{at}unsw.edu.au

Malignant gliomas are characterized by an intrinsic resistance to apoptosis. Increasing evidence suggests that this is a fundamental mechanism by which gliomas evade elimination when treated with both conventional and targeted therapies. In this review, we describe the multiple anti-apoptotic signals that have been demonstrated to be active in malignant gliomas. We describe the preclinical evidence that suggests that targeting those signaling anomalies can increase tumor responsiveness and enhance the elimination of gliomas in preclinical models. We discuss recent advances in translating pro-apoptotic compounds to clinical trial, and the potential for implementing agents that target the apoptotic pathway as a strategy for improving the outcomes for patients with high-grade gliomas.

Supported by the Royal Australasian College of Physicians Rowden White Fellowship and the Australian-American Fulbright Commission (D.S.Z.); the Hagerty Fund Research Award (A.L.K. and D.S.Z.); and the Stop & Shop Pediatric Brain Tumor Fund and the C.J. Buckley Research Fund (M.W.K.).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.