Potential New Pathway Can Overcome Glioblastoma Resistance

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Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience
Article Date: 25 Jan 2012 - 9:00 PST

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Glioblastoma is the most prevalent and most aggressive malignant brain tumor in humans, and is one of the most resistant to current treatments. Individuals with the disease typically survive around 15 months.

Earlier research concentrated on activating the (apoptosis) cell death pathway through therapeutic agents like tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Most of these experiments were however impeded by resistance.

Chunhai "Charlie" Hao, M.D., Ph.D., a neuropathologist at Emory University explained:

"Scientists in this field have been hoping to treat this cancer with this new type of apoptosis pathway-targeted therapeutic drug, and this new information may provide a path forward."

Hao and his team identified a potential new pathway for targeted therapies by using tumor-initiating cells (cancer stem cells) and human gliblastoma samples.

Frequently TRAIL treatment results in caspase-8-mediated cell death. However, the findings revealed that the A20 E3 ligase is highly expressed in glioblastomas and forms a signaling complex together with receptor interacting protein 1 (RIP1) and caspase-8. When this complex interacted with TRAIL, the researchers noted that the A20 E3 ligase triggered ubiquitination of RIP1, interfering with the activation of caspase-8, and subsequently prevented caspase-8-initiated apoptosis.

Hao, explained:

"Previous research in this area has been unable to overcome the obstacle created by resistance. This research shows one of the mechanisms for how we can manipulate the ubiquitination process to overcome the resistance to the apoptosis-targeted cancer therapies."

It is crucial to understand the mechanisms of resistance in order for developing treatments going forward, said Hao.

Results of the study by Hao and colleagues are published in Cancer Discovery, the latest journal of the American Association for Cancer Research.

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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