Tumour treating fields in a combinational therapeutic approach

Abstract

The standard of care for patients with newly diagnosed Glioblastoma multiforme (GBM) has remained unchanged since 2005, with patients undergoing maximal surgical resection, followed by radiotherapy plus concomitant and maintenance Temozolomide. More recently, Tumour treating fields (TTFields) therapy has become FDA approved for adult recurrent and adult newly-diagnosed GBM following the EF-11 and EF-14 trials, respectively. TTFields is a non-invasive anticancer treatment which utilizes medium frequency alternating electric fields to target actively dividing cancerous cells. TTFields selectively targets cells within mitosis through interacting with key mitotic proteins to cause mitotic arrest and cell death. TTFields therapy presents itself as a candidate for the combinational therapy route due to the lack of overlapping toxicities associated with electric fields. Here we review current literature pertaining to TTFields in combination with alkylating agents, radiation, anti-angiogenics, mitotic inhibitors, immunotherapies, and also with novel agents. This review highlights the observed synergistic and additive effects of combining TTFields with various other therapies, as well highlighting the strategies relating to combinations with electric fields.

Ion Channels as Therapeutic Targets in High Grade Gliomas

“…The Optune™ system developed by Novocure Ltd. (Haifa, Israel) is a novel FDA-approved electrotherapeutic treatment for primary and recurrent adult GBM. The Optune™ device is indicated for patients 22 years and older that have a histologically confirmed case of supratentorial GBM (WHO Grade IV astrocytoma) [ 162 ]. The use of Optune™ as a therapy is approved in combination for patients who have received maximal surgical resection and with those who have received concomitant TMZ and radiotherapy [ 163 ].…”

“…A review by Branter et al reveals that there are clear indications for TTF as a combinatorial therapy with both mainstay and novel therapeutics, however there is limited efficacy when used as a monotherapy. Despite there being some descriptive mechanistic preclinical evidence there is a significant lack of study into the mechanism of TTF in complex models [ 162 ].…”

Barium Titanate Nanoparticles Sensitise Treatment-Resistant Breast Cancer Cells to the Antitumor Action of Tumour-Treating Fields

“…Although there is an accumulating body of evidence demonstrating enhanced efficacy of the combined treatment of TTFields and chemotherapeutic agents or radiotherapy 1,2,9,[11][12][13][14][15][16][17][18]29 , not much is known about TTFields-responsive sensitisers. Here, we report novel TTFields-responsive sensitisers, BTNPs, characterised by high dielectric constants.…”

“…Many preclinical and clinical studies indicate that TTFields would be applicable for other tumour types including breast, lung, pancreatic, and ovarian cancers 4,6,7,9,10 . Early clinical trials have shown that only TTFields treatment for GBM patients was not significantly better than conventional chemotherapy 3,9,[11][12][13] . However, recent preclinical studies suggest that combination therapy of TTFields with conventional treatments including chemotherapy, immunotherapy, and radiotherapy are more effective than TTFields monotherapy in GBM 1,2,9,[11][12][13][14][15][16][17][18] .…”

The Molecular Effects of Ionizing Radiations on Brain Cells: Radiation Necrosis vs. Tumor Recurrence

“…In general, in the case of brain tumors surgical resection is the first step when possible and only then radiation therapy follows with or without combined chemotherapy [31]. RT planning is based upon neuroimaging, which must be as precise as possible in order to minimize radiation damage to healthy tissues [32]. In this scenario, MRI represents the gold standard thanks to its excellent anatomic detail and spatial resolution although there are some limitations after RT treatment.…”