title: Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo.
abstract: Long-term survival rates for advanced ovarian cancer patients have not changed appreciably over the past four decades; therefore, development of new, effective treatment modalities remains a high priority. Tumor Treating Fields (TTFields), a clinically active anticancer modality utilize low-intensity, intermediate frequency, alternating electric fields. The goal of this study was to evaluate the efficacy of combining TTFields with paclitaxel against ovarian cancer cells in vitro and in vivo. In vitro application of TTFields on human ovarian cancer cell lines led to a significant reduction in cell counts as compared to untreated cells. The effect was found to be frequency and intensity dependent. Further reduction in the number of viable cells was achieved when TTFields treatment was combined with paclitaxel. The in vivo effect of the combined treatment was tested in mice orthotopically implanted with MOSE-LTICvcells. In this model, combined treatment led to a significant reduction in tumor luminescence and in tumor weight as compared to untreated mice. The feasibility of effective local delivery of TTFields to the human abdomen was examined using finite element mesh simulations performed using the Sim4life software. These simulations demonstrated that electric fields intensities inside and in the vicinity of the ovaries of a realistic human computational phantom are about 1 and 2 V/cm pk-pk, respectively, which is within the range of intensities required for TTFields effect. These results suggest that prospective clinical investigation of the combination of TTFields and paclitaxel is warranted.
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Tali
authors: T
authors: Voloshin
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Mijal
authors: M
authors: Munster
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Roni
authors: R
authors: Blatt
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Anna
authors: A
authors: Shteingauz
authors: Department of Biomedical Sciences and Pathobiology and Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA, 24061.
authors: Paul C
authors: PC
authors: Roberts
authors: Department of Biomedical Sciences and Pathobiology and Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA, 24061.
authors: Eva M
authors: EM
authors: Schmelz
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel. mosheg@novocure.com.
authors: Moshe
authors: M
authors: Giladi
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Rosa S
authors: RS
authors: Schneiderman
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Einav
authors: E
authors: Zeevi
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Yaara
authors: Y
authors: Porat
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Ze'ev
authors: Z
authors: Bomzon
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Noa
authors: N
authors: Urman
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Aviran
authors: A
authors: Itzhaki
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Shay
authors: S
authors: Cahal
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Eilon D
authors: ED
authors: Kirson
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Uri
authors: U
authors: Weinberg
authors: Novocure Ltd. Topaz Building, MATAM center, Haifa, 31905, Israel.
authors: Yoram
authors: Y
authors: Palti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy; D017239:Paclitaxel / Q000494:pharmacology*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D017239:Paclitaxel
keywords: combination therapy; ovarian cancer; paclitaxel; tumor treating fields