A novel EGFR-TKI inhibitor (cAMP-H(3)BO(3)complex) combined with thermal therapy is a promising strategy to improve lung cancer treatment outcomes

PURPOSE: Although EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors) induce favorable responses as first-line non-small cell lung cancer treatments, drug resistance remains a serious problem. Meanwhile, thermal therapy also shows promise as a cancer therapy strategy. Here we combine a novel EGFR-TKI treatment with thermal therapy to improve lung cancer treatment outcomes. RESULTS: The results suggest that the cAMP-H(3)BO(3) complex effectively inhibits EGFR auto-phosphorylation, while inducing apoptosis and cell cycle arrest in vitro. Compared to the negative control, tumor growth was significantly suppressed in mice treated with oxidative phosphorylation uncoupler thyroxine sodium and either cAMP-H(3)BO(3) complex or cAMP-H(3)BO(3) complex (P < 0.05). Moreover, the body temperature increase induced by treatment with thyroxine sodium inhibited tumor growth. Immunohistochemical analyses showed that A549 cell apoptosis was significantly higher in the cAMP-H(3)BO(3) complex plus thyroxine sodium treatment group than in the other groups. Moreover,Ca(2+) content analysis showed that the Ca(2+) content of tumor tissue was significantly higher in the cAMP-H(3)BO(3) complex plus thyroxine sodium treatment group than in other groups. MATERIALS AND METHODS: Inhibition of EGFR auto-phosphorylation by cAMP and cAMP-H(3)BO(3) complex was studied using autoradiography and western blot. The antitumor activity of the novel EGFR inhibitor (cAMP-H(3)BO(3) complex) with or without an oxidative phosphorylation uncoupler (thyroxine sodium) was investigated in vitro and in a nude mouse xenograft lung cancer model incorporating human A549 cells. CONCLUSIONS: cAMP-H(3)BO(3) complex is a novel EGFR-TKI. Combination therapy using cAMP-H(3)BO(3) with thyroxine sodium-induced thermal therapy may improve lung cancer treatment outcomes.