Opportunities and challenges of using circulating tumor DNA to predict lung cancer immunotherapy efficacy
Shanshan Li1,2, Ting Yuan2, Jing Yuan3
1School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.
Abstract:
Immune checkpoint inhibitors (ICIs), particularly anti-programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) antibodies, have led to significant progress in lung cancer treatment. However, only a minority of patients have responses to these therapies. Detecting peripheral blood of circulating tumor DNA (ctDNA) allows minimally invasive diagnosis, characterization, and monitoring of lung cancer. ctDNA has potential to be a prognostic biomarker and a predictor of the response to ICI therapy since it can indicate the genomic status and tumor burden. Recent studies on lung cancer have shown that pretreatment ctDNA analysis can detect residual proliferative disease in the adjuvant immunotherapy setting and evaluate tumor burden in patients with metastatic disease. Early ctDNA dynamics can not only predict the clinical outcome of ICI therapy but also help distinguish between pseudoprogression and real progression. Furthermore, in addition to quantitative assessment, ctDNA can also detect genetic predictors of response to ICI therapy. However, barriers still exist in the application of ctDNA analysis in clinical lung cancer treatment. The predictive value of ctDNA in lung cancer immunotherapy requires further identification and resolution of these challenges. This review aims to summarize the existing data of ctDNA analysis in patients receiving immunotherapy for lung cancer, understand the limitations of clinical treatment, and discuss future research directions.
Insights
Circulating tumor DNA (ctDNA) shows promise as a biomarker for predicting lung cancer patient response to immune checkpoint inhibitors (ICIs). Further research is needed to overcome challenges and fully integrate ctDNA analysis into clinical practice.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Diagnostics
Background:
- Immune checkpoint inhibitors (ICIs), specifically anti-PD-1/PD-L1 antibodies, have advanced lung cancer treatment.
- Response rates to ICIs in lung cancer remain limited, necessitating improved predictive biomarkers.
Purpose of the Study:
- To review the current data on circulating tumor DNA (ctDNA) analysis in lung cancer patients undergoing immunotherapy.
- To identify challenges and discuss future research directions for ctDNA's clinical application in lung cancer immunotherapy.
Main Methods:
- Review of existing studies on ctDNA analysis in lung cancer immunotherapy.
- Analysis of ctDNA's role in diagnosis, characterization, monitoring, prognosis, and prediction of ICI response.
Main Results:
- ctDNA analysis offers minimally invasive monitoring and characterization of lung cancer.
- Pretreatment ctDNA can detect residual disease and evaluate tumor burden, while early ctDNA dynamics predict outcomes and differentiate pseudoprogression.
- ctDNA can identify genetic predictors of ICI response.
Conclusions:
- ctDNA holds significant potential as a prognostic and predictive biomarker for lung cancer immunotherapy.
- Barriers to the clinical application of ctDNA analysis persist and require further investigation and resolution.
