Review: Using ctDNA to Map Resistance Mechanisms to Targeted Therapy in NSCLC
This Perspective in Nature Reviews Clinical Oncology evaluates how circulating tumour DNA is being used to detect acquired resistance to targeted therapies in advanced NSCLC. The authors review published methodologies, highlight major inconsistencies between studies, and identify key unresolved challenges that limit clinical utility. The work calls for standardised ctDNA approaches to enable more informative clinical trials.
The original study
Utilizing ctDNA to discover mechanisms of resistance to targeted therapies in patients with metastatic NSCLC: towards more informative trials.
- Authors
- Ernst SM, Aldea M, von der Thüsen JH, de Langen AJ, Smit EF, Paats MS, et al.
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Review
- PMID
- 40087401
Original abstract
Advances in targeted therapies for patients with non-small-cell lung cancer have substantially improved the outcomes of those with actionable alterations in certain oncogenic driver genes. However, acquired resistance to these targeted therapies remains a major challenge. Understanding the mechanisms underlying acquired resistance will be crucial for the development of strategies that might either overcome this effect or delay the onset. Circulating tumour DNA, owing to the need for only minimally invasive sampling and a potential role as both a prognostic and predictive biomarker, is increasingly being used in both research and clinical practice. Several studies have explored the landscape of acquired resistance to targeted therapies using this approach. However, the methodologies of the published studies vary widely, and several major challenges remain in addressing the practical difficulties associated with these methods. These challenges currently limit the depth of research insight provided by the available data. In this Perspective, we review clinical reports describing the use of circulating tumour DNA to detect mechanisms of acquired resistance to targeted therapies, predominantly in patients with advanced-stage non-small-cell lung cancer, and highlight key unresolved questions with the aim of moving towards more-informative research studies.