Combination therapy of Doxorubicin with TTFields and radiation: newer approaches to combat lung cancer

Background: Tumor-treating fields (TTFields) have been used singly or with chemoradiation for treating glioblastoma and mesothelioma but not yet for lung cancer. Survival rates in lung cancer remain abysmal despite advances in early diagnosis and targeted therapies. Aims and objectives: We aimed to investigate the effectiveness of TTFields in inhibiting lung cancer growth and metastasis, as well as the therapeutic effectiveness of TTFields alongside radiation and chemosensitivity-enhancing agents in an in vitro model. Methods: We generated TTFields yielding 0-800 V sine wave signals, 0.9 V/cm applied electric field intensity, and 150 kHz frequency. The human lung cancer cell lines A549 and H460 were used in this study. Cell viability, colony formation, cell death detection, and cell invasion assays were performed to assess the therapeutic effectiveness of TTFields; sensitization of lung cancer cells to TTFields by doxorubicin (DOX); and the combined effect of TTFields, DOX, and irradiation (IR). Results: Lung cancer cells showed a nearly 20% decrease in cell viability at 1 V/cm and 150 kHz. In A549 and H460 cells, TTFields increased apoptosis through increased cleaved caspase3, hindered cell migration and invasion, and improved chemosensitivity to DOX. The combination of DOX and TTFields showed better antitumor results than those of each individually. However, the DOX/TTFields/IR combination was most effective in reducing the viability and migration of lung cancer cells. Conclusion: TTFields as an adjuvant therapy offers probability for improving lung cancer patient outcomes.

Automated summary

This study investigated the effectiveness of TTFields in inhibiting lung cancer growth and metastasis, as well as the therapeutic effectiveness of TTFields alongside radiation and chemosensitivity-enhancing agents. The results showed that TTFields can inhibit lung cancer cell growth and migration, improve chemosensitivity, and have the potential to improve patient outcomes.