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

J Proteome Res. 2025 Aug 2. doi: 10.1021/acs.jproteome.5c00385. Online ahead of print.

ABSTRACT

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have transformed lung adenocarcinoma (LUAD) treatment in EGFR-mutant (MT) patients, but strategies targeting wild-type (WT) EGFR tumors remain necessary. This study analyzed a diverse LUAD patient cohort with EGFR mutation statuses and wild-type profiles for ALK and KRAS to identify stage-specific biomarkers. Using quantitative proteomics and multiomics, we discovered 21 dysregulated proteins in early-stage EGFR-WT LUAD, identifying myeloid-derived growth factor (MYDGF) as a key candidate biomarker. Elevated MYDGF levels in tissue (n = 117) and serum (n = 196) correlated significantly with cancer stage in EGFR-WT patients but not EGFR-MT cases. Notably, a higher tumor-to-normal MYDGF ratio predicted a favorable prognosis in early-stage EGFR-WT LUAD. Functional studies demonstrated that MYDGF exerts distinct roles in cell viability and migration depending on its cellular localization and the invasive potential of cancer cells. Specifically, secreted MYDGF promoted a protumorigenic phenotype, whereas excess intracellular MYDGF appeared to suppress the oncogenic capacity of aggressive cancer cells. MYDGF knockdown and subsequent proteomic analysis provided further insights into these context-dependent functions. These findings highlight EGFR status- and stage-specific proteomic profiles in LUAD, emphasizing the importance of context-dependent biomarker assessment for personalized treatment strategies.

PMID:40752010 | DOI:10.1021/acs.jproteome.5c00385