RESUMEN
Glycogen synthase kinase3 (GSK3), a serine/threonine kinase, is involved in a broad range of pathological processes including cancer. GSK3 has two isoforms, GSK3α and GSK3ß, and GSK3ß has been recognized as a therapeutic target for the development of new anticancer drugs. The present study aimed to investigate the antitumor effects of 9ING41, which is a maleimidebased ATPcompetitive small molecule GSK3ß inhibitor active in patients with advanced cancer. In renal cancer cell lines, treatment with 9ING41 alone induced cell cycle arrest and apoptosis, and autophagy inhibitors increased the antitumor effects of 9ING41 when used in combination. Treatment with 9ING41 potentiated the antitumor effects of targeted therapeutics and increased the cytotoxic effects of cytokineactivated immune cells on renal cancer cell lines. These results provided a compelling rationale for the inclusion of patients with renal cancer in studies of 9ING41, both as a single agent and in combination with current standard therapies.