Tumor Treating Fields and Combination Therapy in Management of Brain Oncology

Abstract

Glioblastoma (GBM) remains a challenging cancer to treat with limited effective therapies. Standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, offer marginal survival benefits but are often limited by side effects and drug resistance. Temozolomide is the most commonly used chemotherapy; however, resistance and lack of efficacy in recurrent GBM hinder its success. Tumor treating fields (TTFields), a novel non-invasive modality that utilizes alternating electric fields, have recently emerged as a promising treatment for GBM. TTFields work by disrupting the function of the mitotic spindle and inducing apoptosis in cancer cells. They can be especially effective when combined with other therapies. TTFields enhance drug delivery when paired with chemotherapy by increasing the permeability of the blood-brain barrier and cell membranes, leading to more effective tumor inhibition. Similarly, TTFields increase cancer cell sensitivity to radiation therapy and improve the efficacy of targeted therapies, such as sorafenib and immunotherapy, particularly in extra-cranial tumors. The Optune device, the primary medical device for TTFields' delivery, offers a convenient and versatile treatment option, allowing remote care and exhibiting fewer adverse effects. This review discusses the potential of TTFields as a valuable addition to GBM treatment, particularly in combination therapies, and highlights the device's clinical applications.

Keywords: brain cancer; glioblastoma; tumor combination therapy; tumor survival; tumor treating fields (TTF).

Figure 1

Effects of TTFields on cancer cell biology.

Figure 2

TTField portable therapeutic device—second-generation Optune^® system.