DNA methylation cooperates with genomic alterations during non-small cell lung cancer evolution.

Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data.

Unveiling Macrophage Content as a Predictive Biomarker for Intraoperative ICG Imaging Efficacy in Lung Cancer.

Due to the phenotypic and genotypic heterogeneity of tumors, the efficacy of intraoperative indocyanine green (ICG) imaging in lung cancer exhibits significant inter-patient variability. This study identifies macrophage content as a critical predictive biomarker for ICG imaging outcomes, offering both mechanistic, and clinical insights into this variability. Mechanistically, macrophages are demonstrated to serve as the principal ICG reservoirs in tumor tissues, exhibiting seven-fold higher uptake capacity compared to cancer cells.

Evaluation of clinical and safety outcomes of cancer vaccines in patients with advanced non-small cell lung cancer after first-line therapy: a systematic review and meta-analysis.

Background: Despite numerous randomized controlled trials (RCTs) on cancer vaccines, systematic evaluations of their efficacy and safety for patients with advanced non-small cell lung cancer (NSCLC) following first-line therapy remain lacking.

Methods: In this systematic review and meta-analysis (PROSPERO, CRD42024568178), PubMed, Cochrane Library, and Embase databases were searched from inception up to December 27, 2024. Published phase II or III RCTs reporting survival outcomes in advanced or metastatic NSCLC patients who received vaccine therapy after first-line therapy were included.

Theranostics targeting fibroblast activation protein in the pan-cancer field.

Fibroblast activation protein (FAP), a membrane-bound glycoprotein overexpressed in cancer-associated fibroblasts (CAFs), is a promising target for diagnostic and therapeutic interventions in oncology. Its elevated expression correlates with tumor progression and metastasis, with minimal presence in normal tissues. Recent advancements in FAP-targeted theranostics have focused on positron emission tomography/computed tomography (PET/CT), fluorescence imaging, and targeted radionuclide therapy (TRT).

Organoid models in oncology: advancing precision cancer therapy and vaccine development.

Organoids are three-dimensional stem cell-derived models that offer a more physiologically relevant representation of tumor biology compared to traditional two-dimensional cell cultures or animal models. Organoids preserve the complex tissue architecture and cellular diversity of human cancers, enabling more accurate predictions of tumor growth, metastasis, and drug responses. Integration with microfluidic platforms, such as organ-on-a-chip systems, further enhances the ability to model tumor-environment interactions in real-time.

Liquid biopsy-based multi-cancer early detection: an exploration road from evidence to implementation.

Current cancer screening methods are limited in scope, often detecting only a few cancer types with low positive predictive value and suboptimal patient adherence. In recent years, liquid biopsy-based multi-cancer early detection (MCED) has emerged as a promising approach to revolutionize cancer control. Despite several MCED tests reaching clinical trial phases and seeking regulatory approval, none have yet been approved for clinical use, highlighting uncertainties regarding their efficacy and applicability.

Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinical translation.

Loss of FTSJ3 promotes R-loop-associated DNA damage and facilitates chemosensitivity in lung cancer cells.

R-loop accumulation has emerged as a critical factor that induces DNA damage and compromises genomic integrity. However, the regulatory mechanisms governing the R-loop-induced DNA damage remain unclear. Here, FTSJ3 was determined to be a pivotal regulator of R-loop homeostasis and genomic stability.

Prognostic Significance, Radiological, and Metabolic Characteristics of Metastatic Lymph Nodes in Resectable Non-Small Cell Lung Cancer Following Neoadjuvant Chemoimmunotherapy.

Background: Metastatic lymph nodes (mLNs) exhibit different responses to neoadjuvant immunotherapy compared to the primary tumor (PT) in non-small cell lung cancer (NSCLC). Evaluating mLNs' response is crucial for predicting treatment efficacy and prognosis; however, such assessments are currently insufficient.

Methods: We enrolled 101 NSCLC patients with mLNs who underwent neoadjuvant chemoimmunotherapy followed by surgery.

Artificial intelligence driven 3D reconstruction for enhanced lung surgery planning.

The increasing complexity of lung surgeries necessitates the need for enhanced imaging support to improve the precision and efficiency of preoperative planning. Despite the promise of 3D reconstruction, clinical adoption remains limited due to time constraints and insufficient validation. To address this, we evaluate an artificial intelligence-driven 3D reconstruction system for pulmonary vessels and bronchi in a retrospective, multi-center multi-reader multi-case study.

Multidisciplinary expert consensus on diagnosis and treatment of multiple lung cancers.

The rising incidence of multiple lung cancers (MLCs), encompassing multiple primary lung cancers (MPLCs) and intrapulmonary metastasis (IPM), poses two significant clinical challenges. First, distinguishing between MPLC and IPM remains difficult due to insufficiently accurate criteria and ambiguous integration of genetic testing. Second, standardized therapeutic protocols are still lacking.

Next-Generation Sequencing vs. Clinical-Pathological Assessment in Diagnosis of Multiple Lung Cancers: A Systematic Review and Meta-Analysis.

Accurately distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastasis (IPM) is crucial for tailoring treatment strategies and improving patient outcomes. While molecular methods offer significant advantages over traditional clinical-pathological evaluations, they lack standardized diagnostic protocols and validated prognostic value. This study systematically compared the diagnostic and prognostic performance of molecular methods versus clinical-pathological evaluations in diagnosing multiple lung cancers (MLCs), specifically focusing on the impact of next-generation sequencing (NGS) parameters on diagnostic accuracy.

Engineered circular RNA-based DLL3-targeted CAR-T therapy for small cell lung cancer.

Purpose: Circular RNA (circRNA) has emerged as a promising RNA therapeutic molecule due to its enhanced stability and prolonged protein expression compared to messenger RNA (mRNA). Using circRNA to construct transient Chimeric Antigen Receptor (CAR)-T cells can mitigate the limitations of conventional viral vector-based CAR-T approaches, such as complex process and long-term side effects.

Methods: The study first reconfirmed the advantageous properties of circRNA, focusing on its stability and protein expression efficiency.

Validation for revision of the stage IIIA(T1N2) in the forthcoming ninth edition of the TNM classification for lung cancer.

Objectives: The 9th edition of the lung cancer tumor-node-metastasis (TNM) staging system downgrades certain non-small cell lung cancer (NSCLC) patients from stage IIIA (T1N2) to IIB(T1N2a). This study aimed to externally validate this stage adjustment.

Methods: Consecutive resected stage IIB and IIIA (the 9th edition of lung cancer TNM staging manual) NSCLC patients were included.

Optimizing the NGS-based discrimination of multiple lung cancers from the perspective of evolution.

Next-generation sequencing (NGS) offers a promising approach for differentiating multiple primary lung cancers (MPLC) from intrapulmonary metastasis (IPM), though panel selection and clonal interpretation remain challenging. Whole-exome sequencing (WES) data from 80 lung cancer samples were utilized to simulate MPLC and IPM, with various sequenced panels constructed through gene subsampling. Two clonal interpretation approaches primarily applied in clinical practice, MoleA (based on shared mutation comparison) and MoleB (based on probability calculation), were subsequently evaluated.

Nicotinamide N-methyltransferase negatively regulates metastasis-promoting property of cancer-associated fibroblasts in lung adenocarcinoma.

Background: Recurrence and metastasis remain significant challenges in lung adenocarcinoma (LUAD) after radical resection. The mechanisms behind the recurrence and metastasis of LUAD remain elusive, and deregulated cellular metabolism is suspected to play a significant role. This study explores the metabolic and epigenetic regulation mediated by nicotinamide N-methyl transferase (NNMT) in LUAD.

Synthetic circRNA therapeutics: innovations, strategies, and future horizons.

Small molecule drugs are increasingly emerging as innovative and effective treatments for various diseases, with mRNA therapeutics being a notable representative. The success of COVID-19 vaccines has underscored the transformative potential of mRNA in RNA therapeutics. Within the RNA family, there is another unique type known as circRNA.

The current therapeutic cancer vaccines landscape in non-small cell lung cancer.

Currently, conventional immunotherapies for the treatment of non-small cell lung cancer (NSCLC) have low response rates and benefit only a minority of patients, particularly those with advanced disease, so novel therapeutic strategies are urgent deeded. Therapeutic cancer vaccines, a form of active immunotherapy, harness potential to activate the adaptive immune system against tumor cells via antigen cross-presentation. Cancer vaccines can establish enduring immune memory and guard against recurrences.

Efficacy of neoadjuvant chemo-immunotherapy in non-small cell lung cancer: a real-world, multicenter, retrospective study.

Background: Resectable non-small cell lung cancer (NSCLC) patients have a high risk of recurrence. Multiple randomized controlled trials (RCTs) have shown that neoadjuvant chemo-immunotherapy brings new hope for these patients. The study aims to evaluate the safety, surgery-related outcomes and oncological outcomes for neoadjuvant chemo-immunotherapy in real-world setting with a large sample size and long-term follow-up.