Expert Rev Anticancer Ther. 2025 Aug 18. doi: 10.1080/14737140.2025.2549538. Online ahead of print.

ABSTRACT

INTRODUCTION: In the era of precision medicine, molecular biomarker testing is increasingly becoming standard of care for Non-Small Cell Lung Cancer (NSCLC) patients. Tissue and liquid biopsy-based Next-Generation Sequencing (NGS) is now highly recommended.

AREAS COVERED: Different NGS platforms emerged as a cost-effective strategy to perform a massive and parallel sequencing performing higher technical sensitivity than old generation technologies in detecting low abundant alterations in challenging diagnostic samples. NGS systems can detect single nucleotide variants (SNV), small insertions and deletions (indels), copy number alterations (CNAs) and structural variants (SVs) or gene fusions across selected druggable genes optimizing clinical administration of NSCLC patients. The diagnostic implementation of the most adequate NGS panel depending on several factors that could impact on the clinical utility of testing assay.

EXPERT OPINION: Promising advanced technologies are emerging as potentially integrative tools in personalized medicine. In this context, multi-omic evaluation including genomic, transcriptomic, fragmentomic and epigenomic signatures are under investigation to significantly modify clinical algorithm of NSCLC patients. On this basis, sequencing strategies may play a pivotal role in the implementation of a new predictive model for cancer diagnosis and prognosis.

PMID:40823981 | DOI:10.1080/14737140.2025.2549538

Future Oncol. 2025 Aug 5:1-19. doi: 10.1080/14796694.2025.2542051. Online ahead of print.

ABSTRACT

Lung Cancer (LC) remains the leading cause of cancer-related mortality. While Tissue Biopsy (TB) remains the gold standard for molecular profiling, its invasiveness and inability to provide real-time monitoring have led to the adoption of Liquid Biopsy (LB) as a minimally invasive alternative. By analyzing different circulating analytes such as cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), Circulating Tumor Cells (CTCs), Extracellular Vesicles (EVs), and Tumor-Educated Platelets (TEPs), LB offers a dynamic approach to assessing tumor heterogeneity, Minimal Residual Disease (MRD), and treatment resistance. Recent clinical trials have underscored their role in guiding therapy decisions and monitoring treatment response. In early-stage disease, several Randomized Clinical Trials (RCTs) have shown that ctDNA clearance predicts survival benefits in patients receiving neoadjuvant or perioperative Immune Checkpoint Inhibitors (ICIs). Additionally, adjuvant RCTs have confirmed the ctDNA prognostic role in post-surgical relapse risk assessment. Despite its transformative potential, challenges such as assay standardization, sensitivity limitations in early-stage disease, and regulatory barriers remain. As ongoing research continues to validate its clinical utility, LB is poised to become an indispensable tool in the precision management of LC.

PMID:40762271 | DOI:10.1080/14796694.2025.2542051

Per Med. 2025 Apr 21:1-10. doi: 10.1080/17410541.2025.2494982. Online ahead of print.

ABSTRACT

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, with most cases diagnosed at advanced stages, resulting in poor survival rates. Early detection significantly improves outcomes, yet current screening methods, such as low-dose computed tomography (LDCT), are limited by high false-positive rates, radiation exposure, and restricted eligibility criteria. This review highlights the transformative potential of genomic and molecular technologies in advancing the early detection of LC. Key innovations include liquid biopsy tools, such as circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) analysis, which offer minimally invasive approaches to detect tumor-specific genetic and epigenetic alterations. Emerging biomarkers, including methylation signatures, cfDNA fragmentomics, and multi-omics profiles, demonstrate improved sensitivity and specificity in identifying early-stage tumors. Advanced platforms like next-generation sequencing (NGS) and machine-learning algorithms further enhance diagnostic accuracy. Integrated approaches that combine genomic data with LDCT imaging and artificial intelligence (AI) show promise in addressing current limitations by improving risk stratification and nodule characterization. The review also explores multi-cancer early detection assays and precision diagnostic strategies tailored for diverse at-risk populations. By leveraging these advancements, clinicians can achieve earlier diagnoses, reduce unnecessary procedures, and ultimately decrease LC mortality.

PMID:40255184 | DOI:10.1080/17410541.2025.2494982

Cytopathology. 2025 Apr 11. doi: 10.1111/cyt.13485. Online ahead of print.

ABSTRACT

The advent of personalised and precision medicine has radically modified the management and the clinical outcome of cancer patients. However, the expanding number of predictive, prognostic, and diagnostic biomarkers has raised the need for simple, noninvasive, quicker, but equally efficient tests for molecular profiling. In this complex scenario, the adoption of liquid biopsy, particularly circulating tumour DNA (ctDNA), has been a real godsend for many cancer patients who would otherwise have been denied the benefits of targeted treatments. Undeniably, ctDNA analysis has several advantages over conventional tissue-based analysis. One advantage is that it can guide treatment decision making, especially when tissue samples are scarce or totally unavailable. Indeed, a simple blood test can inform clinicians on patients' response or resistance to targeted therapies, help them monitor minimal residual disease (MRD) after surgical resections, and facilitate them with early cancer detection and interception. Finally, an equally important advantage is that ctDNA analysis can help decipher temporal and spatial tumour heterogeneity, a mechanism highly responsible for therapeutic resistance. In this review, we gathered and analysed current evidence on the clinical usefulness of ctDNA analysis in solid tumours.

PMID:40219616 | DOI:10.1111/cyt.13485