The Mechanisms of Action of Tumor Treating Fields

Abstract

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of action.

Figure 1.

Biological and biophysical effects of TTFields.

Figure 2.

Dose–response curves (electric field strength vs. % of control) for TTFields applied to four tumor cell types, replicated from Kirson and colleagues (1), curve-fit and extrapolated to show electric field amplitudes predicted to kill 100% of target cells. Quadratic curve-fits show a possible correspondence with the linear-quadratic theory of radiotherapy and similarly, imply two mechanisms of action at low vs. high amplitudes, which may relate to cell cycle phase at which TTFields coincide in asynchronous populations. A, Rat glioma. B, Human non–small lung cell carcinoma. C, Human breast cancer. D, Mouse melanoma (poor fit at low amplitudes due to lack of data points compared with the other curves).