1419-EFHD2 Drives DNA Repair in Radioresistant Cancer

This research identifies a critical regulatory axis involving hsa-let-7b-5p, the protein EFHD2, and lactate metabolism that drives radioresistance and immune evasion in colorectal cancer. The study demonstrates that EFHD2 facilitates DNA damage repair and promotes an immunosuppressive tumor microenvironment by enhancing lactate production and stabilizing HIF-1α. Specifically, lactylation of EFHD2 at the K9 site is essential for its role in maintaining homologous recombination and helping cancer cells survive radiation. Furthermore, the accumulation of lactate reshapes the immune landscape by promoting M2 macrophage polarization and increasing regulatory T cell infiltration while suppressing antitumor T cells. Integrated single-cell and spatial transcriptomics validate that targeting the EFHD2 axis can restore therapeutic sensitivity. Consequently, combining EFHD2 inhibition with immune checkpoint blockade offers a promising strategy to overcome treatment resistance and improve patient outcomes.References:Yu Y, Wu H, Xiao Y, et al. EFHD2 drives lactate-mediated DNA damage repair and immunosuppression via HMGB1 and HIF-1α to confer radioresistance in colorectal cancer[J]. Cell Death & Disease, 2026.前往小宇宙评论区与主播互动