Histone/Lysine Acetylation as a Target for Sensitization in Head and Neck Squamous Cell Carcinoma
CREBBP and EP300, encoding for CBP and p300 respectively, are highly homologous multifunctional histone/lysine acetyltransferases (HATs or KATs) that are mutated in ∼15% of Head and Neck Squamous Cell Carcinoma (HNSCC) and these mutations are associated with clinical recurrence and poorer survival following radiation. We found that some of these mutations demonstrate gain-of-function (GOF) related to increased HR-mediated DNA damage repair (DDR). We hypothesi ze that targeting GOF mutations in HATs/KATs sensitizes HNSCC through induction of a BRCA-like phenotype with decreased DNA repair, increased sensitivity to PARP inhibition, and enhanced immunogenic cell death through a synthetic lethal interaction.
Source: International Journal of Radiation Oncology * Biology * Physics - Category: Radiology Authors: B. Leibowitz, A. Hefner, S. Basu, A. Gopalkrishnan, M. Elfayoumi, C. Pickering, H.D. Skinner Tags: 225 Source Type: research
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