A novel EGFR-TKI inhibitor (cAMP-H3BO3 complex) combined with thermal therapy is a promising strategy to improve lung cancer treatment outcomes

Abstract

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-H₃BO₃ 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-H₃BO₃ complex or cAMP-H₃BO₃ 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-H₃BO₃ complex plus thyroxine sodium treatment group than in the other groups. Moreover,Ca²⁺ content analysis showed that the Ca²⁺ content of tumor tissue was significantly higher in the cAMP-H₃BO₃ complex plus thyroxine sodium treatment group than in other groups.

Materials and Methods: Inhibition of EGFR auto-phosphorylation by cAMP and cAMP-H₃BO₃ complex was studied using autoradiography and western blot. The antitumor activity of the novel EGFR inhibitor (cAMP-H₃BO₃ 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-H₃BO₃ complex is a novel EGFR-TKI. Combination therapy using cAMP-H₃BO₃ with thyroxine sodium-induced thermal therapy may improve lung cancer treatment outcomes.