Associating Patient Responses with Drug Sensitivity in Non-Small Cell Lung Carcinoma Using an Immunoassay on Patient-Derived Cell Cultures

TL;DR

This study uses patient-derived cell cultures and an immunoassay to predict drug responses in non-small cell lung cancer, aiming to improve personalized treatment strategies.

Contribution

The novel contribution is the use of an immunoassay on patient-derived cultures to correlate drug sensitivity with clinical outcomes in NSCLC.

Findings

NSCLC cells showed significant variability in drug responses, with stromal cells being more sensitive.

Stage IV tumors exhibited greater resistance compared to stages I-III.

Etoposide and paclitaxel sensitivity correlated with progression-free survival.

Abstract

Background/Objectives: Non-small cell lung carcinoma (NSCLC) is characterized by its diverse molecular profiles and varying responses to treatment, highlighting the importance of precision medicine in optimizing therapeutic outcomes. A promising approach involves using patient-derived cellular models, which provide insights into the unique biology of individual tumors and their responsiveness to treatment. Methods: We established short-term primary cell cultures from thirteen patients with NSCLC of different subtypes and stages, including both cancer and stromal cells. To evaluate the ex vivo cytotoxicity and selectivity of eight chemotherapeutics and erlotinib, we employed an immunoassay, and the results were analyzed using an automated imaging system. Scoring of the obtained results was also performed. The ex vivo responses to cisplatin, etoposide, and paclitaxel were correlated with the patients’ responses to therapy. We used Kaplan–Meier analysis to assess progression-free survival (PFS) differences among patient groups. Results: NSCLC cells exhibited significant variability in their responses to drugs, with stromal cells demonstrating greater sensitivity. Tumors at stages I-III responded to multiple treatments, whereas stage IV cells showed considerable resistance. Erlotinib effectively reduced cancer cell growth at lower doses but plateaued at higher concentrations. The immunoassay indicated 67% sensitivity and 100% specificity in predicting patient responses to chemotherapy. Sensitivity to etoposide and paclitaxel correlated with progression-free survival (PFS). Conclusions: A personalized treatment strategy, such as our immunoassay based on the ex vivo responses of cancer patients’ cells, can guide treatment decisions and, in some cases, serve as surrogate biomarkers for tumor types that lack actionable biomarkers.

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