Preclinical data showed that human mesothelioma cells are highly sensitive to TTFields2
- Given that MPM is usually contained within the thorax, the addition of a loco-regional modality like NovoTTF-100L could be of benefit in this setting, especially if associated with low toxicity2
- TTFields are low-intensity (1-3 V/cm) alternating electric fields tuned to a specific frequency (150 kHz) to disrupt solid tumor cancer cell division1
- TTFields disrupt cell division through physical interaction with key molecules during mitosis3
NovoTTF-100L delivers TTFields to selectively disrupt mitosis1,4
- Impair microtubule assembly
- Impede midline localization of cytokinetic band
- Induce cytoplasmic blebbing and mitotic failure
- Cause asymmetric chromosome segregation
- Induce intracellular dielectrophoresis of macromolecules and organelles
Learn more about the TTFields mechanism of action
NovoTTF-100L has the same mechanism of action as Optune®, which was approved for recurrent glioblastoma (GBM) in 20111,7,8
TTFields, Tumor Treating Fields.
References: 1. NovoTTF-100L Instructions For Use for Unresectable Malignant Pleural Mesothelioma. Novocure 2019. 2. 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. 3. Toms SA, Kim CY, Nicholas G, Ram Z. Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial. J Neurooncol. 2019;141(2):467-473. 4. Kirson ED, Dbalý V, Tovarys F, et al. Proc Natl Acad Sci USA. 2007:104(24):10152-10157. 5. Gutin PH, Wong ET. Noninvasive application of alternating electric fields in glioblastoma: a fourth cancer treatment modality. Am Soc Clin Oncol Educ Book. 2012:126-131. 6. Gera N, Yang A, Holtzman TS, Lee SX, Wong ET, Swanson KD. Tumor Treating Fields perturb the localization of septins and cause aberrant mitotic exit. PLoS ONE. 2015;10(5):e0125269. doi:10.1371/journal.pone.0125269. 7. Summary of Safety and Effectiveness Data (SSED). US FDA Website. https://www.accessdata.fda.gov/cdrh_docs/pdf10/ p100034s013b.pdf. Accessed April 9, 2019. 8. Optune Instructions For Use for GBM. Novocure 2019. 9. FDA Approves the NovoTTF-100L™ System in Combination with Chemotherapy for the Treatment of Malignant Pleural Mesothelioma [press release]. St. Helier, Jersey: Business Wire; May 23, 2019. 10. Novocure Corporate presentation. https://www.novocure.com/wp-content/uploads/ 2019/01/201901_NVCR_Corporate_Presentation_vF-1.pdf. Published January 2019. Accessed April 16, 2019. 11. US Food and Drug Administration. Premarket Approval (PMA) Database. Silver Spring, MD: US Department of Health and Human Services; 2015. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P100034S013. Updated May 13, 2019. Accessed May 16, 2019.