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.