An overview of the preclinical and clinical studies of the effects of tumor treating fields on malignant glioma cells
DOI:
https://doi.org/10.15584/ejcem.2017.2.7Keywords:
anaplastic astrocytoma, glioblastoma multiforme, brain tumor, tumor treating fields, tumor therapyAbstract
Anaplastic astrocytoma (AA, WHO grade III) and glioblastoma multiforme (GBM, WHO grade IV) are malignant tumors of the brain. The average survival time of patients with GMB is approximately one year and two years in the case of anaplastic astrocytoma with standard therapy based on surgical tumor resection followed by chemotherapy or radiotherapy. High invasiveness of gliomas, the ability of rapid division and so-called diffusive infiltration of tumor cells into normal brain tissue, which prevents complete surgical removal, are hallmarks of theses tumors. Therefore, new specific therapies for eliminating cancer cells are needed to treat this tumors. Recently, it has been demonstrated that alternating electric field, also known as tumor treating fields (TTFields) has a unique mechanism of destroying glioma cells. TTFields applies electromagnetic energy frequency-dependent and intensitydependent and disrupts cancer cell replication as they undergo mitosis. Futhermore, TTFields turn out to act comparably to conventional chemotherapeutics, lacking numerous side adverse associated with chemotherapy. The authors provide an up-todate review of the mechanism of action as well as preclinical and clinical data on TTFields.Downloads
References
Merz F, Gaunitz F, Dehghani F, et al. Durante M, Bechmann I. Organotypic slice cultures of human glioblastoma reveal different susceptibilities to treatments. Neuro Oncol. 2013;15:670-681.
Hasller MR, Sax C, Flechl B, et al. Thialomide as palliative treatment in patients with advanced secondary glioblastoma. Oncology. 2015;88:173-179.
Marlon GS, Santoshi K. Efficiacy and safety of trating glioblastoma with tumor-treating fields therapy. Clin J Oncol Nurs. 2016;20:9-13.
Omuro AM, Faivre S, Raymond E. Lessons learned in the development of targeted therapy for malignant gliomas. Mol Cancer Ther. 2007;6:1909-1919.
Hester GL. Electric and magnetic fields: managing and uncertain risk. Environment. 1992;34:7-31.
McCann J, Dietrich F, Rafferty C, Martin AO. A critical review of the genotoxic potential of electric and magnetic fields. Mutat Res. 1993;297:61-95.
McCann, Dietrich F, Rafferty C. The genotoxic potential of electric and magnetic fields: an update. Mutat Res. 1998;411:45-86.
Kirson ED, Gurvich Z, Schneiderman R, et al. Disruption of cancer cell replication by alternating electric field. Cancer Res. 2004;64:3288-3295.
Kirson ED, Dbalý V, Tovarys F, et al. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007;104:10152-10157.
Tailibert S, Le Ruhn E, Chamberlain M. Tumor trating fields: a new standard treatment for glioblastoma? Curr Opin Neurol. 2015;28:659-664.
Kirson ED, Schneiderman RS, Dbalý V, et al. Chemotherapeutic treatment efficiacy and sensitivity are increased by adjuvant alternating electric field (TTFields). BMC Med Phys. 2009;9:1.
Pless M, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of tumor treating fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer (NSCLC). Lung Cancer. 2013;81:445-450.
Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Exp Opin Invest Drugs. 2011;20:1099-1106.
Swanson KD, Lok E, Wong ET. An overview of alternating electric fields therapy (NovoTTF Therapy) for the treatment of malignant glioma. Curr Neurol Neurosci Rep. 2016;16:8.
Gera N, Yang A, Holtzman T, Lee SX, Wong ET, Swanson KD. Tumor treating fields perturb the localization of septins and cause aberrant mitotic exit. PLOS One. 2015;10:e0125269. doi: 10.1371/journal.pone.0125269.
Giladi M, Schneiderman RS, Voloshin T, et al. Mitotic spindle disruption by alternating electric fields leads to improper chromosome segregation and mitotic catastrophe in cancer. Cells Sci Rep. 2015;5:18046:2–16.
Yvon AM, Wadsworth P, Jordan MA. Taxol suppresses dynamics of individual mictrotubules in living human tumor cells. Mol Biol Cell. 1990;10:947-959.
Lowe J, Li H, Downing KH, Nogales E. Refined structure of alpha beta-tubulin at 3.5 A resolution. J Mol Biol. 2001;313:1045-1057.
Felder CE, Prilusky J, Silman I, Sussman JL. A server and database for dipole moments of proteins. Nucleic Acids Res. 2007;35:512-521.
Albertson R, Cao J, Hiseh TS, Sullivan W. Vesicles and actin are targeted to the cleavage furrow via furrow microtubules and the central spindle. J Cell Biol. 2008;181:777-790.
D’Aviono PP, Savoian MS, Glover DM. Cleavage furrow formation and ingression during animal cytokinesis: a microtubule legacy. J Cell Sci. 2005;118:1549-1558.
Gilden J, Krummel MF. Control of cortical rigidity by the cytoskeleton: emerging roles for septins. Cytoskeleton (Hoboken). 2010;67:477-486.
Gilden JK, Peck S, Chen YC, Krummel MF. The septin cytoskeleton facilitates membrane retraction during motility and blebbing. J Cell Biol. 2012;196:103-114.
Bowen JR, Hwang D, Bai X, Roy D, Spiliotis ET. Septin GTPases spatially guide microtubule organization and plus end dynamics in polarizing epithelia. J Cell Biol. 2011;194:187-197.
Gutin PH, Wong ET. Noninvasive application of alternating electric fields in glioblastoma: a fourth cencer treatment modality. Am Soc Clin Oncol Educ Book. 2012:126-31.
Hottinger A, Pacheco P, Stupp R. Tumor treating fields: a novel treatment modality and its use in brain tumors. Neuro Oncol. 2016;18:1338-1349.
Wick W, Puduvalli VK, Chamberlain MC, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010;28:1168–1174.
Batchelor TT, Mulholland P, Neyns B, et al. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013;313212–13218.
Yung WK, Albright RE, Olson J, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000;83:588–593.
Stupp R, Taillibert S, Kanner AA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015;314:2535–2543.
Stupp R, Wong ET, Scott C, et al. NT-40 interim analysis of the EF-14 trial: a prospective, multicenter trial of NOVOTTF-1ooA together with temozolomide compared to temozolomide alone in patients with newly diagnosed GMB. Neurooncology. 2014;16:167.
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