Akt3 Protein Makes Brain Tumor Resistant To Treatment

MedicalResearch.com Interview with:
Kristen Turner PhD. (first author) and
Wei Zhang, Ph.D. Professor
Department of Pathology
Director, Cancer Genomics Core Lab
University of Texas MD Anderson Cancer Center
Houston, Texas 77030

Medical Research: What is the background for this study? What are the main findings?

Response: Glioblastoma (GBM) is the most commonly diagnosed type of brain tumor and is among the most aggressive and challenging cancer types to treat. The traditional approaches to combat this pervasive cancer include surgery combined with radiation and chemotherapy (temozolomide); yet, most will succumb to the disease in just over one year.

In this study, we investigated the Akt family of proteins that are known to be highly active in the majority of Glioblastoma cases. We compared each Akt family member and its ability to initiate glioma progression. We discovered that activation of the third Akt member (Akt3) led to glioma progression and very aggressive tumors. We then studied these tumors to compare their molecular attributes and found evidence of increased DNA repair. Finally, we discovered that the Akt3-induced DNA repair function led to increased survival of Glioblastoma cells after treatment with the DNA damaging agents, radiation and temozolomide.

Medical Research: What should clinicians and patients take away from your report?

Response: Some Glioblastomas may resist standard treatment approaches due to amplified Akt3 and the resulting increased DNA repair capacity. A molecular screen for Akt3 should be performed prior to treatment. Akt3 amplification may indicate that the standard treatment will be less effective and alternative strategies should be considered.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: Given that Akt3 is a dominant player in glioma progression and aids in tumors resisting therapy, inhibitors should be developed and tested that specifically block Akt3 function. Additionally, testing the standard therapy in conjunction with DNA repair inhibitors in tumors with amplified Akt3 should be investigated.

Citation:

Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1414573112

 

MedicalResearch.com Interview with:,Kristen Turner PhD. (first author) and, & Wei Zhang, Ph.D. Professor (2015). Akt3 Protein Makes Brain Tumor Resistant To Treatment
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