Associating Patient Responses with Drug Sensitivity in Non-Small Cell Lung Carcinoma Using an Immunoassay on
Ana Podolski-Renić1, Sofija Jovanović Stojanov1, Dragana Marić2,3
1Department of Neurobiology, Institute for Biological Research "Siniša Stanković"-National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia.
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.
Insights
This study shows that an immunoassay using patient-derived non-small cell lung carcinoma (NSCLC) cells can predict chemotherapy response, aiding personalized treatment strategies for lung cancer patients.
Area of Science:
- Oncology
- Translational Medicine
- Cancer Biology
Background:
- Non-small cell lung carcinoma (NSCLC) exhibits molecular heterogeneity, necessitating precision medicine for optimal treatment.
- Patient-derived cellular models offer valuable insights into individual tumor biology and drug responsiveness.
Purpose of the Study:
- To establish and evaluate patient-derived primary cell cultures from NSCLC patients.
- To assess the ex vivo cytotoxicity and selectivity of various chemotherapeutics and erlotinib.
- To correlate ex vivo drug responses with patient outcomes and progression-free survival.
Main Methods:
- Established short-term primary cell cultures from 13 NSCLC patients.
- Utilized an immunoassay and automated imaging to evaluate drug cytotoxicity.
- Correlated ex vivo drug responses (cisplatin, etoposide, paclitaxel) with patient therapy responses.
- Employed Kaplan-Meier analysis for progression-free survival (PFS) assessment.
Main Results:
- Significant variability in NSCLC cell drug responses observed; stromal cells were more sensitive.
- Stage IV NSCLC cells showed resistance, while stages I-III responded to multiple treatments.
- The immunoassay demonstrated 67% sensitivity and 100% specificity in predicting patient chemotherapy response.
- Etoposide and paclitaxel sensitivity correlated with improved PFS.
Conclusions:
- Ex vivo drug response assays using patient cells can guide personalized NSCLC treatment decisions.
- This immunoassay approach can serve as a surrogate biomarker for tumors lacking actionable targets.
- Personalized medicine strategies based on ex vivo drug sensitivity hold promise for optimizing NSCLC therapy.
