BMC Med Res Methodol. 2026 Mar 9. doi: 10.1186/s12874-026-02821-4. Online ahead of print.

NO ABSTRACT

PMID:41803732 | DOI:10.1186/s12874-026-02821-4

Cancer Treat Res Commun. 2026 Mar 2;47:101162. doi: 10.1016/j.ctarc.2026.101162. Online ahead of print.

ABSTRACT

BACKGROUND: The collection of clinical data and patient tumor specimens in institutional repositories is essential to accelerate translational research in lung cancer, linking laboratory findings with patient outcomes. These resources allow investigators to explore tumor heterogeneity, analyze therapeutic profiles and, more recently, generate patient-derived models of cancer. Given the plethora of therapies in clinical use or under investigation, it is critical to establish tissue collection programs that support the identification of predictive biomarkers of drug sensitivity to define patient subgroups that may benefit from tailored therapeutic strategies. However, access to high-quality viable specimens remains limited.

METHODS: We established a multidisciplinary program -the Lung Cancer Tissue Collection (LCTC) study- to prospectively collect viable human specimens and clinical data. Samples can be collected post-diagnosis and at multiple treatment time points, preserving material for future studies.

RESULTS: In the first 24 months of the LCTC study, we enrolled 158 patients and collected over 700 specimens from patients with lung cancer. EGFR and KRAS mutations were the most frequently identified oncogenic drivers, mirroring frequencies reported in public datasets. We achieved a 60 % success rate in cryopreservation -measured by the proportion of patient-derived organoids growing after tissue thawing and processing- highlighting the feasibility of our program.

CONCLUSIONS: The LCTC biobank captures the molecular and clinical diversity of lung cancer, providing a clinically annotated resource of viable tissue and longitudinal blood specimens. This platform enables patient-derived modeling and multi-omic and functional studies to investigate tumor biology, treatment response, and resistance, supporting biomarker discovery and precision medicine.

PMID:41797251 | DOI:10.1016/j.ctarc.2026.101162

Int J Clin Oncol. 2026 Mar 6. doi: 10.1007/s10147-026-03001-6. Online ahead of print.

ABSTRACT

BACKGROUND: Early detection of cancer and precise recurrence monitoring remain major unmet needs in oncology. Conventional screening is limited to a few cancer types, leaving nearly half of cancers without established programs. Multi-cancer early detection (MCED) tests based on circulating tumor biomarkers have shown promise, but sensitivity for early-stage remains a challenge. In parallel, detection of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) has emerged as a powerful prognostic and predictive tool, though current assays remain limited in sensitivity and specificity. This study aims to integrate multi-omics data to develop more refined and highly sensitive MCED and MRD assays.

METHODS: This study leverages clinical information and biospecimens from patients with cancer and cancer-naïve individuals. Samples from patients with cancers will be derived from the MONSTAR-SCREEN-3 study, while those from cancer-naïve individuals will be obtained from the Tohoku Medical Megabank Project. Comprehensive analyses will include whole-genome sequencing (WGS), whole-exome sequencing (WES), whole-transcriptome sequencing (WTS), proteomics, metabolomics, and microbiome profiling using stool and saliva. Artificial intelligence (AI)-based multi-omics integration will be performed to develop novel MCED and MRD assays and to evaluate their clinical performance. The primary endpoints are the sensitivity and specificity of MCED and MRD assays.

DISCUSSION: This is the first large-scale study to integrate comprehensive multi-omics profiling with AI for MCED and MRD assay development. The findings are expected to advance precision oncology by improving early diagnosis and recurrence monitoring.

TRIAL REGISTRATION: UMIN000053815, approved by the Institutional Review Board of the National Cancer Center Hospital East.

PMID:41790338 | DOI:10.1007/s10147-026-03001-6

MedComm (2020). 2026 Mar 2;7(3):e70656. doi: 10.1002/mco2.70656. eCollection 2026 Mar.

ABSTRACT

Chemotherapy is the mainstay in the treatment of advanced gastric cancer (GC); yet, GC showed diverse responses to first-line chemotherapy regimens and the underlying molecular basis is still not clear. Here, we established a system that combined organoid-based chemotherapy regimen screening and transcriptome-based evaluation to identify underlying molecular signatures of different responses to chemotherapy. We generated 19 GC patient-derived organoids (PDOs) from surgically resected specimens with corresponding histological characteristics of parent tumors and tested all of the five most commonly used first-line chemotherapy regimens. Based on the treatment responses, PDOs were classified into double-sensitive, single-sensitive, and not-sensitive groups. PDOs that responded well to chemotherapy presented high expression levels of the P53 pathway genes and low expression levels of cell proliferative activity genes. Furthermore, the chemotherapy-based tumor classification of GC was established. The GC tumor classification was verified by multi-omics features from the TCGA dataset and public drug response datasets. In conclusion, this study systematically evaluated clinical chemotherapy regimens for GC and identified chemotherapy response-associated molecular signatures based on human GC organoids, which are beneficial to the precise treatments of GC.

PMID:41782964 | PMC:PMC12954136 | DOI:10.1002/mco2.70656

Diagnostics (Basel). 2026 Feb 9;16(4):523. doi: 10.3390/diagnostics16040523.

ABSTRACT

Background: Liquid biopsy, particularly through the analysis of circulating tumor DNA (ctDNA), represents a significant advancement in oncology. Unlike traditional tissue biopsies, ctDNA offers a minimally invasive, real-time approach to cancer management. It has demonstrated considerable potential in early cancer detection, monitoring of therapeutic responses, and assessing minimal residual disease (MRD) to predict recurrence. By enabling comprehensive molecular profiling through a simple blood test, ctDNA supports the core principles of precision oncology, facilitating more personalized and adaptive treatment strategies. Methods: In the following article we describe the recent developments focused on refining ctDNA detection assays to improve sensitivity and specificity. Advanced technologies, including next-generation sequencing (NGS) and digital PCR, are commonly employed. The integration of artificial intelligence (AI) and multi-omics approaches-such as combining genomic, epigenomic, and transcriptomic data-has further enhanced the analytical power of ctDNA assays. Results: Emerging evidence shows that ctDNA-based liquid biopsy enables dynamic, real-time tracking of tumor evolution and therapeutic resistance. Clinical studies have demonstrated its efficacy in detecting early-stage cancers, guiding treatment selection, and predicting relapse with higher accuracy than some conventional methods. Moreover, AI-enhanced algorithms have improved signal detection, allowing for more precise and earlier identification of actionable mutations and MRD. Conclusions: ctDNA analysis via liquid biopsy is poised to revolutionize cancer care by offering a non-invasive, precise, and adaptive tool for tumor characterization and monitoring. Although obstacles remain-particularly regarding assay sensitivity, standardization, and economic feasibility-ongoing technological innovations and multi-omics integration are rapidly advancing its clinical viability. With continued progress, ctDNA-based liquid biopsy is likely to become a cornerstone of routine oncology practice.

PMID:41750672 | PMC:PMC12938931 | DOI:10.3390/diagnostics16040523

bioRxiv [Preprint]. 2026 Feb 18:2026.02.18.706515. doi: 10.64898/2026.02.18.706515.

ABSTRACT

The recurrence rate following complete surgical resection of primary non-small cell lung cancer is as high as 55%, yet no approach currently exists to evaluate the risk of local recurrence. The premetastatic paradigm is the recognition that metastasis is preceded by reprogramming naïve tissues to prime a microenvironment for tumor cell survival and subsequent reactivation. Identification of biomarkers of the pre-metastatic niche would allow us to evaluate a patient's risk of local relapse in the normal lung parenchyma surrounding the resected tumor. We designed a workflow incorporating in vivo modelling, radiology, and deep learning-guided three-dimensional (3D) imaging, spatial proteomics, and transcriptomics to identify previously unreported signals associated with the early transformation of the lung parenchyma announcing regional metastasis. We curated biorepository spanning timepoints before and after resection of primary Lewis Lung Carcinoma (LLC) tumors. Using radiology and cellular resolution 3D histology, we calculated the number and distribution of metastases in mouse lungs and developed an algorithm to guide placement of spatial proteomics and transcriptomics to regions containing early micro-metastases and the pre-metastatic microenvironment. Molecular and tissue features associated with presence, size, and location of metastases guided the identification of both myeloid (F4/80) and senescent (p16/p21) cell signatures in the premetastatic and metastatic environments. Finally, multiparametric flow cytometry of metastatic lungs in a senescence reporter GEMM (tdTomato-p16 INKA mice) resolved senescent cells including alveolar macrophages as the cellular phenotypes associated with these early premetastatic signatures. Altogether, this work highlights a novel AI-assisted approach for detection of biomarkers of tissue remodeling during lung cancer invasion.

PMID:41756853 | PMC:PMC12934922 | DOI:10.64898/2026.02.18.706515

Innovation (Camb). 2025 Aug 6;7(1):101076. doi: 10.1016/j.xinn.2025.101076. eCollection 2026 Jan 5.

ABSTRACT

Although circulating cell-free DNA (cfDNA) methylation has emerged as the mainstream approach in multi-cancer detection blood tests (MCDBTs), the potential of integrating proteins and mutations, to enhance its performance remains unclear. The PROMISE study (NCT04972201) was conducted to investigate the feasibility of a multi-omics integration strategy in MCDBTs across nine types of cancers in head and neck (excluding nasopharynx), esophagus, lung, stomach, liver, biliary tract, pancreas, colorectum, and ovary. Blood samples were prospectively collected from 1,706 participants (840 non-cancer; 866 cancer) and then randomly divided into training and validation sets. The complementarity between various omics were investigated, and specific omics features were carefully selected for further multimodal model construction. The methylation-based classifier outperformed both the mutation-based and protein-based classifiers. As 95.0% of cancer cases detected by the mutation-based classifier were simultaneously identified by the methylation-based classifier, while 14.0% of the protein-positive samples were missed, protein markers may provide complementary value to the methylation-based classifier. Compared with the methylation-based classifier, the multimodal classifier combining methylation and protein features exhibited an improved sensitivity of 75.1% (95% confidence interval [CI], 69.3%-80.3%) at the same specificity of 98.8% with the accuracy of top predicted origin (TPO1) of 73.1% (95% CI, 66.2%-79.2%). Notably, the TPO1 accuracy reached 100% in liver and ovarian cancers with negative results of the methylation-based classifier. Collectively, these data suggest that the integration of protein markers in the multimodal classifier can offer additional benefits to the methylation-based classifier, particularly in identifying liver and ovarian cancers.

PMID:41737326 | PMC:PMC12925926 | DOI:10.1016/j.xinn.2025.101076

Mol Aspects Med. 2026 Feb 23;108:101461. doi: 10.1016/j.mam.2026.101461. Online ahead of print.

ABSTRACT

Diabetes mellitus (DM) is a significant risk factor for several cancers, particularly cancers of the liver, pancreas, and endometrium. This review aims to understand the connections between diabetic pathophysiology and cancer biology. We synthesize how core metabolic disturbances-hyperinsulinemia, hyperglycemia, and inflammation-promote tumorigenesis by dysregulating canonical oncogenic pathways such as IGF-1 signaling, DNA damage repair, and immunometabolism. Subsequently, we focus on how key molecular integrators-such as p38 MAPK, Wnt/β-catenin, and the AGEs-RAGE axis-mediate metabolic stress to confer proliferative and invasive advantages to tumor cells. However, a direct translational application of these mechanisms, particularly in the context of repurposing antidiabetic drugs for cancer therapy, remains challenging due to inconsistent clinical outcomes. To address this gap, we suggest that a fundamental shift in approach is required. We propose that future research must move beyond simple pathway categorization and instead utilize spatial analysis techniques to reveal how diabetic metabolites reshape the tumor microenvironment (TME). By integrating single-cell and spatial omics technologies, the field can begin to map the precise cellular niches within tumors where diabetic metabolites exacerbate malignant progression and foster treatment resistance. This perspective is essential for developing targeted strategies to mitigate cancer risk and improve outcomes for the expanding population of patients with DM and cancer.

PMID:41734405 | DOI:10.1016/j.mam.2026.101461

Future Oncol. 2026 Feb 20:1-14. doi: 10.1080/14796694.2026.2631302. Online ahead of print.

ABSTRACT

Gastric cancer (GC) is an epithelial malignant tumor with high morbidity and mortality. In recent years, more and more studies have strengthened our understanding of how GC develops, including the origin of GC cells, precancerous lesions, gene mutations, transcriptional changes, protein translation and the tumor microenvironment. With the concept of accurate tumor therapy gradually applied to clinical practice, these data provide more reference and basis for early prevention, early screening, early detection and accurate treatment of GC.

PMID:41717787 | DOI:10.1080/14796694.2026.2631302

Int J Mol Sci. 2026 Feb 6;27(3):1597. doi: 10.3390/ijms27031597.

ABSTRACT

Ampullary carcinoma (AC) is a rare gastrointestinal malignancy with dual intestinal and pancreatobiliary differentiation, complicating diagnosis, staging, and treatment. This review synthesizes current epidemiology, pathology, and multi-omic data to outline a pragmatic care pathway: lineage-first at presentation, mutation-fast at progression. Histology remains the primary classifier: the intestinal subtype generally aligns with colorectal regimens, whereas pancreatobiliary and mixed subtypes favor pancreaticobiliary therapy. In selected fit patients, modified FOLFIRINOX may address mixed phenotypes. Next-generation sequencing adds precision by identifying therapeutically relevant alterations, including ERBB2/HER2 amplifications, MSI-high/dMMR, BRAF V600E, and rare NTRK or RET fusions, while KRAS mutations are enriched in pancreatobiliary tumors. We recommend early application of a rapid-core panel (KRAS/BRAF, MSI/dMMR, ERBB2/HER2, RNA-based fusions) to capture high-impact targets, followed by comprehensive profiling at first progression. Liquid biopsy, plasma circulating tumor DNA (ctDNA), or bile-derived DNA may complement tissue and help identify the dominant lineage. Research priorities include ampulla-enriched umbrella trials, explicit AC subcohorts in tissue-agnostic studies, and ctDNA-informed endpoints. This lineage-first, mutation-fast paradigm supports precision care and evidence generation in AC.

PMID:41684016 | PMC:PMC12897727 | DOI:10.3390/ijms27031597

Transl Cancer Res. 2026 Jan 31;15(1):43. doi: 10.21037/tcr-2025-1499. Epub 2026 Jan 27.

ABSTRACT

BACKGROUND: Osteoglycin (OGN), an extracellular matrix protein, has emerging but poorly characterized roles in cancer. This study presents the first pan-cancer investigation of OGN's expression patterns, clinical significance, immune interactions, and functional mechanisms.

METHODS: Multi-omics data from Genotype Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), The Cancer Genome Atlas (TCGA), and Human Protein Atlas (HPA) databases were integrated. Differential expression was analyzed in normal tissues and tumor samples. Diagnostic utility was evaluated using area under the curve (AUC) of receiver operating characteristic (ROC) curve. Prognostic value was assessed via Kaplan-Meier [overall survival (OS); disease-specific survival (DSS); disease free interval (DFI); progression-free interval (PFI)] and Cox regression analyses. Immune microenvironment correlations were quantified using ESTIMATE, CIBERSORT, and gene set enrichment. Functional pathways were explored through gene set enrichment analysis (GSEA) and correlation with hallmark cancer signatures.

RESULTS: OGN was broadly expressed in normal tissues (brain, liver, kidney) but significantly downregulated in most tumor types (P<0.05, TCGA; validated at protein level, HPA). OGN demonstrated high diagnostic accuracy in pan-cancer (AUC: 0.703-0.990), achieving near-perfect performance in colon adenocarcinoma (COAD) (AUC: 0.966) and thyroid cancer (THCA) (AUC: 0.920). High OGN expression correlated with improved survival outcomes in thymoma (THYM) (OS/DSS) and cholangiocarcinoma (CHOL) (PFI/DFI), but worse prognosis in lung adenocarcinoma​/liver hepatocellular carcinoma​ (LUAD/LIHC), indicating cancer-type specificity. OGN expression strongly associated with immune cell infiltration (macrophages, natural killer cells, T cells), chemokine signaling, programmed death-ligand 1 (PD-L1) levels, microsatellite instability (MSI), and tumor mutation burden (TMB). GSEA revealed enrichment of OGN-linked genes in epithelial-mesenchymal transition (EMT), angiogenesis, JAK-STAT, and PI3K pathways across cancers.

CONCLUSIONS: Our pan-cancer analysis highlights OGN as a context-dependent regulator linking extracellular matrix (ECM) remodeling with immune and angiogenic signaling. Its pan-cancer dysregulation, diagnostic/prognostic value, and crosstalk with immune evasion mechanisms nominate OGN as a promising multi-functional biomarker and therapeutic target.

PMID:41674945 | PMC:PMC12885879 | DOI:10.21037/tcr-2025-1499