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.