Efficacy Evaluation of Adjuvant Therapeutic Drugs Against Early and Middle Stage Non-Small Cell Lung Cancer Organoids

Abstract

30–55% post-surgical recurrent rate of early and middle stage non-small cell lung cancer (e/mNSCLC) suggests the need of adjuvant therapy. The e/mNSCLC derived organoids (e/mNSCLCOs)-based efficacy evaluation of the proposed regimens may improve clinical benefits for e/mNSCLC patients. The e/mNSCLCOs are established from 33 IA-IIIB resectable non-small cell lung cancer (NSCLC) patients without systemic antitumor therapy via optimized 3D culture, of which six with epidermal growth factor receptor (EGFR) mutation. Immunohistochemical staining is employed to ascertain the maintenance of biomarker expression patterns of e/mNSCLCOs with that of their parental tumors. The e/mNSCLCOs are treated with six conventional anti-NSCLC chemotherapeutic regimens, respectively. Calcein-AM/PI cell viability/cytotoxicity assay and EdU cell proliferation test reveal that the platinum-based chemotherapeutic or mono-chemotherapeutic regimens are generally ineffective to e/mNSCLCOs because of their high IC₅₀ values. Non-platinum gemcitabine combined with vinorelbine achieve better anti-e/mNSCLCOs outcome in terms of suppressed cell proliferation and 51.6–65.8% of intra-organoid cell death. The 6 e/mNSCLCOs with EGFR mutations are sensitive to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in drug selective patterns. The low efficacy of conventional anti-NSCLC drugs to e/mNSCLCOs suggests the necessity to explore alternative approaches for better adjuvant management of e/mNSCLC patients.