The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects. Interestingly, DNA-PKcs directly phosphorylated Akt1 at S473 in an in vitro kinase assay but not vice-versa. Pharmacological inhibition of DNA-PKcs or Akt restored radiosensitivity in tumour cells expressing Akt1-E17K or Akt1-TDSD. In conclusion, Akt1-mediated radioresistance depends on its activation state and nuclear localization and is accessible to pharmacologic inhibition.
S. Oeck, K. Al-Refae, H. Riffkin, G. Wiel, R. Handrick, D. Klein, G. Iliakis, and V. Jendrosseka.
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Xstrahl to Highlight Superficial and Orthovoltage Radiotherapy Solutions for Skin Cancer and Selective Benign Conditions at AAPM 2024
Xstrahl, a global leader in the delivery of superficial radiation therapy devices and preclinical radiation research systems, will demonstrate Xstrahl 200, a modern orthovoltage radiotherapy solution for treating superficial lesions, skin cancers, and selective benign conditions at the 66th Annual Meeting & Exhibition of the American Association of Physicists in Medicine (AAPM) in Los Angeles, CA, from July 21-25, 2024, at booth 518.