Personalized drug testing in a patient with non-small-cell lung cancer using cultured cancer cells from pleural effusion

Abstract

Objective Patients with non-small-cell lung cancer (NSCLC) and primary or acquired resistance do not respond to targeted drugs. We explored whether cancer cells can be cultured from liquid biopsies from patients with primary resistance to tyrosine kinase inhibitors (TKIs). We aimed to predict patients’ responses to drugs according to in vitro drug testing results. Methods Cancer cell cultures were established from the pleural effusion of a patient with TKI-resistant NSCLC using a conditional reprogramming technique. Phenotypic drug sensitivity tests were performed using the Cell Counting Kit-8 assay. We tested individual drugs and compared the synergistic and inhibitory effects of drug combinations. Results The results of our in vitro sensitivity test using the combination of cisplatin and pemetrexed were correlated with the patient’s response. Conclusion This represents the first successful report of predictive testing for combination therapy in patients with epidermal growth factor receptor-mutant NSCLC and primary TKI resistance. This strategy should be applicable to both chemotherapies and targeted therapies, and it will significantly improve the clinical treatment and management of patients with NSCLC and primary or acquired resistance to targeted therapies, as well as patients lacking targetable mutations.

Translation Potential and Challenges of In Vitro and Murine Models in Cancer Clinic

“…One critical success factor of CRT is the use of feeder cells and ROCK inhibitors to help tumor cells and other epithelial cells proliferate continuously in vitro ( Figure 1 A) [ 62 , 63 , 64 ]. At present, multiple cancer cells have been established using CRT [ 64 ], including adenoid cystic carcinoma [ 65 ], breast [ 66 ], prostate [ 67 , 68 ], pancreatic [ 69 ], colorectal [ 70 ], lung [ 71 , 72 ], cervical [ 73 ], skin, kidney, ovarian cancers, and so on [ 64 , 74 ]. In addition, conditionally reprogrammed cells can be generated from PDX models and organoids [ 75 , 76 , 77 ] and passaged more than 200 times while preserving the heterogeneity of tumor cells [ 78 , 79 ].…”