Combined In Vitro Ttfields And Paclitaxel Reduce Proliferation And Clonogenicity In Non-Small Cell Lung Cancer (Nsclc) Cells From A Patient Previously Treated With Standard-Of-Care

Abstract TTFields therapy in conjunction with chemotherapy has been FDA approved as a first line treatment regimen for patients with unresectable malignant pleural mesothelioma. Clinical trials are underway to test the efficacy of TTFields in patients with progressive NSCLC or NSCLC brain metastases following standard-of-care or radiosurgery, respectively. Our study utilized tumor cells extracted from a NSCLC metastatic brain tumor from a patient previously treated with standard-of-care chemoradiation prior to progression to brain metastasis. These patient-derived NSCLC cells were subjected to TTFields application with and without paclitaxel to determine if the combination of TTFields with paclitaxel would be more effective than either treatment alone. Written informed consent was obtained from the patient, who was 60 years-old and female. She received concurrent carboplatin/paclitaxel and radiotherapy to the upper lobe of her left lung prior to discovery and resection of a solitary brain lesion. Cells isolated from the metastatic brain tumor were cultured for 3 passages prior to plating on coverslips (4 × 104 each) in DMEM/F12 media with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 kHz. Paclitaxel was added to the media to a final concentration of 5 nM. Cells were treated for 14 days. At the end of the treatment period, some coverslips of cells were lysed and assayed for lactate dehydrogenase (LDH) to represent cell number (n=5) and another set of coverslips of cells were harvested and replated in triplicate for the clonogenic assay (n=3). Groups were compared with one-way ANOVA. Data shown in table are mean ± SD. For the LDH assay, ANOVA p<0.0001. For the clonogenic assay, ANOVA p=0.0003. Overall, the combination of TTFields with paclitaxel produced additive reductions in cell proliferation (75%) and reduced the clonogenic potential (95%) compared to untreated controls. The additive effects of TTFields and paclitaxel suggest that they target different cell populations within a heterogeneous tumor, and that lung cancer patients previously treated with standard-of-care may benefit from TTFields therapy. Proliferation and clonogenic assay results from combined TTFields and paclitaxelAssayControlPaclitaxel (5 nM)TTFieldsTTFields ± Paclitaxel (5 nM)Proliferation (LDH assay)1.83±0.090.81±0.041.34±0.150.46±0.21Clonogenicity (cell counts)26641±46258697±161717399±59981598±598 Citation Format: Sharon K. Michelhaugh, Sandeep Mittal. Combined in vitro TTFields and paclitaxel reduce proliferation and clonogenicity in non-small cell lung cancer (NSCLC) cells from a patient previously treated with standard-of-care [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5254.