2434 - Irradiation-Induced CK2/SUPT16H Axis Modulation Enhances Radiation Resistance in Lung Cancer via DNA Damage Response and Chromatin Remodeling
Presenter(s)
S. You1, Q. Luo2, and R. Meng1; 1Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China, 2Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Wuhan, China
Purpose/Objective(s): We hypothesize that casein kinase 2–mediated SUPT16H upregulation enhances radiation resistance in lung cancer, and that disrupting this axis will improve local tumor control. The primary objective is to evaluate changes in local tumor control rates when combining a small-molecule CK2 inhibitor with radiotherapy in a preclinical model.
Materials/Methods: This ongoing study employs lung cancer cell lines engineered to modulate SUPT16H and CK2 expression. Cells are exposed to escalating radiation doses (2–8 Gy) with or without a selective CK2 inhibitor. DNA damage and repair kinetics are measured via comet assays and ?-H2AX immunofluorescence. Clonogenic assays assess changes in surviving fractions. For in vivo validation, subcutaneous xenografts receive fractionated radiotherapy alone or in combination with CK2 blockade, and tumor volume is tracked for six weeks post-treatment to determine local control. Comprehensive statistical comparisons will be conducted to ascertain synergy between CK2 inhibition and radiotherapy. No data are currently available.
Results: Preliminary results show that inhibition of CK2 led to a significant decrease in SUPT16H expression in lung cancer cells. This reduction in SUPT16H expression was associated with increased radiation sensitivity, as evidenced by a marked decrease in clonogenic survival after irradiation (p<0.05) and an increase in DNA damage, as indicated by comet assay results. These findings suggest that SUPT16H plays a role in mediating radiation resistance in lung cancer cells, and CK2 inhibition can sensitize these cells to radiation.
Conclusion: These initial results demonstrate that the CK2-mediated regulation of SUPT16H is a key factor in modulating radiation sensitivity in lung cancer cells. Targeting CK2 to reduce SUPT16H expression enhances radiation sensitivity, suggesting a potential therapeutic strategy to improve the efficacy of radiotherapy in lung cancer.