Abstract
As with many cancer treatments, tumor treating fields (TTFields) target rapidly dividing tumor cells. During mitosis, TTFields-exposed cells exhibit uncontrolled membrane blebbing at the onset of anaphase, resulting in aberrant mitotic exit. Based on these criteria, at least two protein complexes have been proposed as TTFields’ molecular targets, including α/β-tubulin and the septin 2, 6, 7 heterotrimer. After aberrant mitotic exit, cells exhibited abnormal nuclei and signs of cellular stress, including decreased cellular proliferation and p53 dependence, and exhibit the hallmarks of immunogenic cell death, suggesting that TTFields treatment may induce an antitumor immune response. Clinical trials lead to Food and Drug Administration approval for their treatment of recurrent glioblastoma. Detailed modeling of TTFields within the brain suggests that the location of the tumor may affect treatment efficacy. These observations have a profound impact on the use of TTFields in the clinic, including what co-therapies may be best applied to boost its efficacy.
Highlights
Alternating electric fields therapy is a novel anticancer treatment that disrupts tumor cell mitosis
The first US Food and Drug Administration (FDA)-approved indication is for the treatment of recurrent glioblastoma
While interphase is a highly anisotropic stage, the processes that mitosis depends on possess properties that make them inherently more susceptible to perturbation by electromotive forces introduced into the cell by TTFields. As mitosis proceeds, both the level of order and the demand for spatial and temporal precision of execution by these structures crescendos from assembly of the mitotic spindles to the triggering of the significant biomechanical forces generated by the cytokinetic cleavage furrow (CCF) that is capable of dividing the parental cell into two daughters in only minutes
Summary
Alternating electric fields therapy is a novel anticancer treatment that disrupts tumor cell mitosis. The first US Food and Drug Administration (FDA)-approved indication is for the treatment of recurrent glioblastoma. We will discuss the basic cell biology effects, physics properties, and clinical trial data of this emerging anticancer treatment When TTFields were perpendicular to the plane of division, cells were relatively unaffected but when the TTFields were parallel to the plane of division, cells exhibited a higher degree of
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