Despite optimal radiation therapy (RT), chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC) fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and proteasome inhibition showed synergistic effects. Proteasome inhibition resulted in an 80-90% decrease in homologous recombination (HR), a 50% decrease in expression of NF-κB-inducible HR genes BRCA1 and FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced foci. IκBα RNAi knockdown rescued NSCLC radioresistance. Irradiation of mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly increased murine survival compared to either treatment alone. Proteasome inhibition is a promising strategy for NSCLC radiosensitization via inhibition of NF-κB-mediated expression of Fanconi Anemia/HR DNA repair genes.
Cron KR, Zhu K, Kushwaha DS, Hsieh G, Merzon D, Rameseder J, Chen CC, D’Andrea AD, Kozono D.
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Xstrahl to Highlight Superficial and Orthovoltage Radiotherapy Solutions for Skin Cancer and Selective Benign Conditions at ACRO Summit 2025 in Las Vegas
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. Visit Xstrahl at booth 220 at the ACRO Summit 2025 – The Radiation Oncology Summit located at Planet Hollywood, Las Vegas, NV from March 12-15, 2025.
