bims-metorg 2026-01-18 papers

Issue of 2026–01–18
six papers selected by
Bruna Martins Garcia, CABIMER

J Exp Clin Cancer Res. 2026 Jan 14.

Reconstructing the metastatic journey: functional circulating tumor cells and disseminated tumor cells based models for translational oncology.

Caroline Sanglier, Laure Cayrefourcq, Catherine Alix-Panabières.

Metastatic progression, driven by the dissemination of circulating tumor cells (CTCs) through the bloodstream, remains the leading cause of cancer-related death. A rare subset of CTCs, characterized by tumor-initiating properties and phenotypic plasticity, plays a pivotal role in the formation of distant metastases. The ability of these cells to survive in the circulation, evade the immune surveillance, and establish secondary tumors underscores their biological significance. However, CTC extreme rarity and heterogeneity pose major challenges for their in-depth functional characterization. Disseminated tumor cells (DTCs) are cells that have extravasated and persist in distant organ niches, often in a dormant state, and represent a complementary and equally critical component of metastatic progression. Their capacity to remain quiescent for prolonged periods before reactivation highlights the need to study both CTCs and DTCs to fully understand metastasis initiation and relapse. Recent advances in CTC isolation and culture have led to the development of patient-derived CTC lines and CTC-derived xenograft animal models, offering unprecedented opportunities to investigate metastatic seeding, therapeutic resistance and tumor evolution. CTC- and DTC-based models provide valuable insights into the biology of CTCs from different cancer types, revealing key molecular drivers of metastasis formation and potential therapeutic targets. In this review, we summarize the state-of-the-art methodologies for establishing CTC- and DTC-based models and evaluate their contribution to understand tumor progression and response to treatments. We discuss the current challenges in generating and maintaining these models, including the influence of hypoxic conditions, enrichment strategies, and culture medium optimization. Then, we highlight their potential applications in precision oncology, particularly for biomarker discovery and for preclinical drug testing.

Keywords: CTC; CTC lines; DTC; Liquid biopsy; PDX models

DOI: https://doi.org/10.1186/s13046-025-03617-y

Quant Imaging Med Surg. 2026 Jan 01. 16(1): 93

Clinical and imaging manifestations of metastases from rare sites.

Qian Yang, Nan Chen, Jie Zhang, Jiajia Su, Yong Zhang, Weipeng Yan, Shuixia Zhang.

Because various primary cancers may metastasize to rare sites, metastatic tumors have a wide variety of imaging presentations. Their imaging appearance primarily depends on features related to the primary tumor, such as the degree of tumor differentiation, histopathologic category, tumor markers, and intratumor alterations. In certain clinical situations, imaging features and clinical history may help provide a more accurate diagnosis. Metastatic tumors can involve almost any organ, but the recognition of rare sites of metastasis is insufficient. Because clinical manifestations are heterogeneous and imaging manifestations are atypical, these metastatic tumors can easily be misdiagnosed or missed. Radiology plays an important role in the diagnosis and follow-up of patients with metastatic tumors. Computed tomography (CT) and magnetic resonance imaging (MRI) are the primary imaging modalities used to evaluate metastatic tumors and to differentiate metastatic tumors from other diseases (particularly primary organ tumors or inflammatory conditions). In this study, the principal clinical, histopathological, and imaging characteristics of metastases to uncommon sites were synthesized, with the dual aim of refining organ-specific differential diagnoses and providing a comprehensive overview of the variable manifestations of this rare condition. The marked morphologic heterogeneity of these metastases constitutes a formidable diagnostic challenge. The interpretation of various imaging findings plays a crucial role in the diagnosis and follow-up of patients with metastatic tumors at rare sites and may be critical to informing treatment decisions.

Keywords: Metastases; diagnosis; malignant tumors; radiology; rare sites

DOI: https://doi.org/10.21037/qims-2024-2953

Am J Cancer Res. 2025 ;15(12): 5058-5083

Decoding the metastatic nexus: how chronic stress reprograms neuroendocrine-metabolic-microbiome circuits to fuel tumor metastasis.

Yuxin Wang, Wenchen Sun, Haitao Li, Fei Xu, Wenqiang Cui.

Metastasis, the leading cause of death in patients with solid tumors, involves the spread of cancer cells to distant organs. While genetic and environmental factors contribute, chronic stress is a crucial factor in metastatic progression by disrupting neuroendocrine, immune, metabolic, and microbial homeostasis. This review synthesizes evidence linking chronic stress to tumor metastasis through three pathways: (1) direct effects on tumor cell metabolism, (2) remodeling of the tumor microenvironment, and (3) dysregulation of the gut microbiota. Describe how activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system influence epithelial-mesenchymal transition, immune evasion, and angiogenesis via β-adrenergic and glucocorticoid receptor signaling. Explore how microbial metabolites and barrier dysfunction influence immune and neuroendocrine circuits, creating a pro-metastatic loop. Finally, we highlight therapeutic strategies, including psychological interventions and pharmacologic approaches, to alleviate chronic stress. This review proposes a mechanistic framework linking neuroendocrine signaling, metabolic reprogramming, and the microbiome-immune axis.

Keywords: Chronic stress; gut microbiota; metabolic reprogramming; neuroendocrine regulation; tumor metastasis; tumor microenvironment

DOI: https://doi.org/10.62347/OKKH6279

Breast Cancer Res. 2026 Jan 12. 28(1): 12

Multiomic profiling of ER-positive HER2-negative breast cancer reveals markers associated with metastatic spread.

Sergio Mosquim Junior, Måns Zamore, Johan Vallon-Christersson, Lisa Rydén, Fredrik Levander.

BACKGROUND: Metastatic disease is the main cause of breast cancer (BC)-related deaths, but prediction of metastases remains challenging especially in the large and diverse group with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors. Molecular tumor features beyond currently used markers could provide important information for stratifying metastatic risk. To allow for the discovery of new subtypes and molecular tumor features associated with metastatic spread, i.e., both lymph node and distant metastases, we here leverage advances in proteomic profiling of tumors.
METHODS: We developed a protocol for proteome and phosphoproteome analysis using label-free data independent acquisition (DIA) liquid chromatography tandem mass spectrometry (LC-MS/MS) and integrated the generated data with parallel transcriptome data for the profiling of 182 ER-positive, HER2-negative primary BC tumors from the SCAN-B cohort.
RESULTS: A total of 13,571 protein groups, 7107 phosphopeptides and 13,085 expressed genes were quantified in at least 70% of the samples. The data showed clear differences between invasive lobular carcinoma and no special type cancers, including the hallmark loss of E-cadherin expression and differences in catenin levels. We identified potential new subtypes with differential immune infiltration patterns and survival through unsupervised consensus clustering. Additionally, by adopting an integrative, multiomic data analysis workflow, we identified several potential protein markers of both lymph node and distant metastases. For lymph node metastasis, the level of phosphorylated ES8L2 serine at position 570 (multivariable p value = 0.05, HR = 0.61, 95% CI 0.38-0.99) was associated with improved recurrence-free survival, and showed decreased abundance in lymph node positive cases. For distant metastases, on the other hand, proteins belonging to the heat shock protein 90 family were associated with worse distant recurrence-free survival (multivariable p value = 0.0058, HR = 2.10, 95% CI 1.24-3.55), with significantly higher abundance levels in patients with a distant recurrence event. These correlations with survival could also be validated in multiple external cohorts.
CONCLUSIONS: In summary, we present the most comprehensive matched multiomic dataset from ER-positive/HER2-negative BC tumors, not only serving as an invaluable resource for further advancing precision medicine but also allowing the discovery of potential biomarkers and providing unique insights into metastatic processes.
TRIAL REGISTRATION: Sweden Cancerome Analysis Network-Breast: Genomic Profiling of Breast Cancer (SCAN-B), beginning 2010-08, NCT02306096.

Keywords: Automation; Biomarker discovery; Breast cancer; Deconvolution; Immune infiltration; Mass spectrometry; Metastasis; Multi-omics; Phosphoproteomics; Proteomics

DOI: https://doi.org/10.1186/s13058-025-02173-9

Respir Res. 2026 Jan 15.

Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.

Xing Huang, Huimin Shen, Chenglong Shao, Lei Wang, Xinying Zheng, Yu Wang, Lei Qiu, Shaoyan Zhang, Tong Zhang, Zhenhui Lu.

Keywords: Lung cancer; Metabolic reprogramming; Precision medicine; Targeted therapy; Tumor microenvironment

DOI: https://doi.org/10.1186/s12931-025-03383-7

Mol Biol Evol. 2026 Jan 12. pii: msag008. [Epub ahead of print]

Full spatio-temporal analyses of migration and colonization in evolution - Dense 3D mapping of cancer metastases provides new insights.

Qihang Chen, Senmao Li, Xianrui Wu, Qing Xu, Ranran Zhu, Yongsen Ruan, Ao Lan, Zihan Liu, Jiarui Weng, Yanjiang Zhao, Xiying Xu, Xinyue Qi, Jinhong Lai, Leyi Xiao, Ping Lan, Chung-I Wu, Bingjie Chen.

The process of migration and colonization is important in evolution; for example, modern humans experienced multiple waves of migrations out of Africa. However, no data cover the spatio-temporal patterns sufficiently to be truly informative. Metastatic cancer provides a unique in vivo model to study these processes through rapid somatic evolution. Here, we apply the high-resolution sampling technique (Dense 3D Crypt-scale Sampling) to analyze hundreds of spatially mapped micro-samples from the primary colorectal cancer and liver metastases in two representative cases. This would be analogous to recording the "out-of-Africa" events in two repeats. Our results support that liver metastases arise from polyphyletic and polyclonal seeding events where multiple, genetically distinct clones colonize a new site together. Following colonization, these multi-clonal populations can evolve into distinct spatial architectures: segregated territories formed by cells with low motility, or highly intermixed patterns driven by high motility. The colonization (or seeding) process begins within the first third of the primary tumor's progression, creating a large number of widespread but clinically undetectable micrometastatic colonies. These findings support a model where metastatic competence is not an intrinsic trait of a single "winner" clone but an emergent property of multiple concurrent clones. Collectively, our work supports metastasis as a multi-stage process initiated early in tumor development, characterized by continuous polyclonal dissemination and the formation of spatially distinct clonal architectures. This general pattern may echo the ecology of migration and colonization in organismal evolution.

DOI: https://doi.org/10.1093/molbev/msag008