Therapeutics: Gap junction protein α 1, 43kDa (GJA1; CX43; connexin-43)

Cell culture, mouse and patient sample studies suggest GJA1 inhibitors could help treat temozolomide-resistant glioblastoma. In human glioblastoma cell lines and patient-derived glioblastoma cells, high levels of GJA1 expression correlated with low temozolomide sensitivity. In tumors, high expression of GJA1 correlated with poor survival. In temozolomide-resistant human glioblastoma cell lines, a peptide inhibitor of GJA1 plus temozolomide decreased sphere formation and decreased cell viability compared with either agent alone. In a xenograft mouse model of glioblastoma treated with temozolomide, co-treatment with the GJA1 inhibitor increased tumor sensitivity to temozolomide compared with no co-treatment. Next steps include optimizing the combined delivery of the GJA1 inhibitor and temozolomide to the brain...