BMS-754807 is cytotoxic to non-small cell lung cancer cells and enhances the effects of platinum chemotherapeutics in the human lung cancer cell line A549

Background: Despite progress in targeted therapies, lung cancer remains the leading cause of cancer-related deaths worldwide, with overall patient survival still poor. The type I insulin-like growth factor receptor (IGF-IR) has been identified as a potential target for lung cancer treatment; however, clinical trials thus far have yielded disappointing results. More research is needed to determine which patients might benefit from IGF-IR-targeted therapies and how to best integrate these agents with existing treatments.

Methods: The dual IGF-IR/insulin receptor inhibitor BMS-754807 was tested both alone and in combination with platinum-based chemotherapeutics in two human non-small cell lung cancer (NSCLC) cell lines. Cell survival was assessed using WST-1 assays, and drug interactions were analyzed with Calcusyn software. Proliferation and apoptosis were evaluated through immunofluorescence for phospho-histone H3 and cleaved caspase 3, respectively.

Results: BMS-754807 treatment alone decreased cell survival and wound closure while increasing apoptosis in both lung cancer cell lines. These effects are likely mediated through IGF-IR/IR signaling and, in part, through the PI3K/AKT pathway, as BMS-754807 significantly reduced IGF-IR/IR and AKT phosphorylation in A549 and NCI-H358 cells. Furthermore, combining BMS-754807 with carboplatin or cisplatin resulted in synergistic cytotoxic effects when administered simultaneously to A549 cells.

Conclusions: BMS-754807 shows promise as a therapeutic agent for NSCLC, especially in tumors with high IGF-IR expression.