A new study by scientists at The University of Texas MD Anderson Cancer Center offers clues as to why some brain cancer patients develop resistance to standard treatments including radiation and temozolomide.
“A major obstacle to effective treatment is acquired resistance to treatment,” lead researcher Wei Zhang, PhD, Professor of Pathology, said in a news release. “Enhanced DNA repair can allow these cancer cells to survive, contributing to resistance and tumor recurrence. We have identified Aktr3 as having the ability to robustly stimulate glioma progression.”
Akts are kinases that regulate cell signaling, involved in many bodily processes such as cell growth, cell death, and tumor growth, he explained. Akts are thought to contribute to the development and progression of many cancers including prostate, breast, liver, colorectal, and others; and one form of this protein, Akt3, appears to be especially prevalent in the brain.
The study, published in the March 2nd issue of the Proceedings of the National Academy of Sciences, describe his team's study results showing how Akt3 activates key DNA repair pathways. Akt3 is tied to DNA's “repair panel,” somehow boosting activation of DNA repair proteins, leading to increased DNA repair, and subsequently to cancer treatment resistance, he explained.
“This activation led to enhanced survival of brain tumor cells following radiation or treatment with temozolomide. Our work has potentially broad application to multiple cancer types in which Akt3 is expressed. Blocking this pathway may help prevent or alleviate therapeutic resistance resulting from enhanced DNA repair.”
The study was funded by the National Institutes of Health, the National Cancer Institute, the Goldhirsh Foundation, the Academy of Finland, the Sigrid Juselius Foundation, and the Finnish Funding Agency for Technology and Innovation.
The other coauthors were Kristen Turner, PhD; Youting Sun, PhD; Kirsi Granberg; Limei Hu, MD; David Cogdell; Xinhui Zhou; and Gregory Fuller, MD, PhD, all from MD Anderson's Department of Pathology; and W.K. Alfred Yung, MD, of the Department of Neuro-Oncology. Other participating institutions were Tampere University of Technology in Finland, and the Institute for Systems Biology in Seattle.