title: Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.
abstract: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.
authors.affiliation: Novocure Ltd., Haifa, Israel. Electronic address: mosheg@novocure.com.
authors.forename: Moshe
authors.initials: M
authors.lastname: Giladi
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Weinberg
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Rosa S
authors.initials: RS
authors.lastname: Schneiderman
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Yaara
authors.initials: Y
authors.lastname: Porat
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Munster
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Voloshin
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Blatt
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Cahal
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Aviran
authors.initials: A
authors.lastname: Itzhaki
authors.affiliation: Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Onn
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Eilon D
authors.initials: ED
authors.lastname: Kirson
authors.affiliation: Novocure Ltd., Haifa, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Palti
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D018827:Carcinoma, Lewis Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004599:Electric Stimulation Therapy; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D017239:Paclitaxel; D002945:Cisplatin