Longevity & AgingCXCR2 Receptor Blocks Radiation Sensitization in Hard-to-Treat Head and Neck Cancer
HPV-negative head and neck squamous cell carcinoma (HNSCC) frequently relapses after radiotherapy, partly because irradiation triggers therapy-induced senescence and a pro-survival secretory program (SASP). Researchers tested ABT-263, a Bcl-2/Bcl-xL inhibitor that eliminates senescent cells, in combination with radiation in two radioresistant HNSCC cell lines. In Cal33 cells, ABT-263 promoted apoptosis, reduced senescence, and radiosensitized cells as shown by clonogenic survival assays. In UPCI:SCC040 cells, ABT-263 reduced viability but failed to improve clonogenic radiosensitization because CXCR2—a receptor for SASP-derived chemokines—was upregulated after treatment. Only when CXCR2 was knocked down alongside ABT-263 treatment did radiosensitization occur. DNA damage levels were unchanged, pointing to a survival-signaling rather than DNA-repair mechanism.
