Tumor-Treating Fields: A Fourth Modality in Cancer Treatment

Abstract

Despite major advances in therapy, cancer continues to be a leading cause of mortality. In addition, toxicities of traditional therapies pose a significant challenge to tolerability and adherence. TTFields, a noninvasive anticancer treatment modality, utilizes alternating electric fields at specific frequencies and intensities to selectively disrupt mitosis in cancerous cells. TTFields target proteins crucial to the cell cycle, leading to mitotic arrest and apoptosis. TTFields also facilitate an antitumor immune response. Clinical trials of TTFields have proven safe and efficacious in patients with glioblastoma multiforme (GBM), and are FDA approved for use in newly diagnosed and recurrent GBM. Trials in other localized solid tumors are ongoing. Clin Cancer Res; 24(2); 266-75. Ó2017 AACR.

5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy

“…Adjuvant 5-fluorouracil (5-FU)-based chemotherapy has been applied as standard therapy for patients with stage-III colon cancer following resection [6]. Combination treatment with 5-FU and other chemotherapeutic agents, including leucovorin and oxaliplatin, improved disease-free survival and overall survival [7,8]. However, resistance is common during treatment and remains an unsolved problem in the clinical application [7].…”

“…Recently, tumor-treating fields (TTFields) have shown promise in clinical protocols involving low-intensity, intermediate-frequency, alternating electric fields that are delivered through noninvasive transducer arrays put locoregionally around the tumor [8]. TTFields have received FDA approval for recurrent and newly diagnosed GBM after surgery and radiotherapy with the adjuvant, temozolomide [9][10][11].…”

Estimation of TTFields Intensity and Anisotropy with Singular Value Decomposition: A New and Comprehensive Method for Dosimetry of TTFields

“…In the following sections, I will describe a method for estimating the strength of the uncorrelated field components in any small tissue region and over one entire activation cycle of TTFields. The method provides individual measures of [1] the mean field intensity experienced by a cell dividing in any random direction in a local volume and [2] of the directional preference of efficacy caused by spatial field correlation. The calculations are based on the field distributions obtained using the FE methods described above.…”

“…Tumor-treating fields (TTFields) are a new and effective treatment against glioblastoma (GBM) [1][2][3]. The treatment uses alternating fields (200 kHz for GBM) to inhibit cancer cell division and tumor growth.…”

Simulating the Effect of 200 kHz AC Electric Fields on Tumour Cell Structures to Uncover the Mechanism of a Cancer Therapy

“…TTFields have been observed to kill virtually all tumour cells in vitro and in some animal preparations [1,2]. They have minor side effects, are increasingly prescribed for brain cancer and are in development or clinical trials for a number of other aggressive malignant cell types in humans [3,4]. It was initially believed that TTFields act on highly polar sub-cellular structures, such as tubulin dimers, septin, actin etc., thereby disrupting spindle formation [1].…”