Emerging molecular testing paradigms in non-small cell lung cancer management—current perspectives and recommendations

Advances in molecular testing and precision oncology have transformed the clinical management of lung cancer, especially non-small cell lung cancer, enhancing diagnosis, treatment, and outcomes. Practical guidelines offer insights into selecting appropriate biomarkers and assays, emphasizing the importance of comprehensive testing. However, real-world data reveal the underutilization of biomarker testing and consequently targeted therapies. Molecular testing often occurs late in diagnosis or not at all in clinical practice, leading to delayed or inadequate treatment. Enhancing precision requires adherence to best practices by all health care professionals involved, which can ultimately improve lung cancer patient outcomes. The future of precision oncology for lung cancer will likely involve a more personalized approach, starting increasingly from earlier disease settings, with novel and more complex targeted therapies, immunotherapies, and combination regimens, and relying on liquid biopsies, muti-detection advanced genomic technologies and data integration, with artificial intelligence as a central orchestrator. This review presents the currently known actionable mutations in lung cancer and new upcoming ones that are likely to enter clinical practice soon and provides an overview of established and emerging concepts in testing methodologies. Challenges are discussed and best practice recommendations are made that are relevant today, will continue to be relevant in the future, and are likely to be relevant for other cancer types too.