# Selective antitumor activity of Tumor Treating Fields (TTFields) involving molecular factors in cancer cells and tumor microenvironment

## TL;DR

This paper reviews how electric fields called TTFields can selectively target cancer cells and change the tumor environment, potentially improving cancer treatments.

## Contribution

The paper systematically reviews molecular and preclinical findings on TTFields' mechanisms and their potential for combination therapies.

## Key findings

- TTFields inhibit tumor growth and modulate the tumor microenvironment through molecular processes.
- Combining TTFields with drugs or radiotherapy shows promise for enhanced cancer treatment.
- TTFields can alter immune responses and tumor microenvironment, aiding immunotherapy.

## Abstract

•Multiple factors are involved in tumor sensitivity and resistance to TTFields.•Omics research has revealed molecular processes triggered by TTFields that inhibit tumor growth and modulate the microenvironment.•The complexity of TTFields effects makes it challenging to identify predictive biomarkers.•Co-treatment with TTFields and some anticancer drugs or radiotherapy show promise.•TTFields’ ability to alter the tumor microenvironment and immune response is of therapeutic interest for novel co-treatments.

Multiple factors are involved in tumor sensitivity and resistance to TTFields.

Omics research has revealed molecular processes triggered by TTFields that inhibit tumor growth and modulate the microenvironment.

The complexity of TTFields effects makes it challenging to identify predictive biomarkers.

Co-treatment with TTFields and some anticancer drugs or radiotherapy show promise.

TTFields’ ability to alter the tumor microenvironment and immune response is of therapeutic interest for novel co-treatments.

The local application of low-intensity electric fields at intermediate frequencies (Tumor Treating Fields – TTFields) has emerged as an effective anticancer treatment in conjunction with chemotherapy and immunotherapy for several solid tumors. Despite this progress, the phenotypic and genetic determinants underlying tumor sensitivity to TTFields remain largely unexplored, representing a critical gap in our understanding.

This review provides a comprehensive analysis of preclinical and translational studies describing the cellular factors that influence the anticancer properties of TTFields. An overview of recent omics studies on the complex cellular and molecular processes initiated by TTFields has revealed important mechanisms of action that warrant further investigation for their therapeutic potential.

The goal is to identify effects that can be leveraged to develop rational, synergistic co-treatments with anticancer agents that have complementary modes of action. In particular, the ability of TTFields to modulate the tumor microenvironment and reverse the local and systemic immunosuppression could represent a promising strategy to enhance the efficacy of immunotherapy across different tumor types.

Image, graphical abstract