bims-metorg 2025-11-02 papers

Issue of 2025–11–02
four papers selected by
Bruna Martins Garcia, CABIMER

Nat Genet. 2025 Oct 27.

Cellular states associated with metastatic organotropism and survival in patients with pancreatic ductal adenocarcinoma.

Most patients with localized pancreatic ductal adenocarcinoma (PDAC) experience recurrence after resection. Analysis of 744 patients with resected PDAC revealed that patients with initial isolated liver-metastatic recurrence (n = 100) had significantly worse overall survival than those with initial isolated lung-metastatic recurrence (n = 31). Using single-nucleus RNA sequencing in a representative cohort, we found that transcriptional profiles of primary cancer cells with liver-metastatic recurrence and lung-metastatic recurrence were correlated with those of normal liver and lung parenchymal cells, respectively, suggesting adoption of organ-specific metastatic programs at the primary site. These signatures were confirmed in transcriptomes of PDAC lung and liver metastases, primary lung and liver tumors, and organotropic PDAC xenograft models. These signatures were independent of large genomic events, and analysis of large-scale tumor profiling data showed no genetic alterations predictive of recurrence patterns. Additional analyses suggested that metastatic recurrence may be determined early in tumorigenesis and influenced by tumor-infiltrating immune cells. Thus, pre-existing cellular states within primary tumors appear to guide organ-specific metastatic relapse.

DOI: https://doi.org/10.1038/s41588-025-02345-5

Cancer Lett. 2025 Oct 28. pii: S0304-3835(25)00674-3. [Epub ahead of print]635 218102

Biomechanical networks of the pre-metastatic niche: Decoding biophysical determinants of tumor metastatic organotropism.

Zichen Guo, Jingyang Liu, Minpu Zhang, Wenfu Zheng, Jing Zhuang, Changgang Sun.

In the metastatic cascade, biomechanics acts as an invisible engine that drives tumor malignancy. Shaping the intrinsic mechanical microenvironment of cancer cells facilitates their distant colonization and metastasis. Mechanical cues serve as physical fingerprints that orchestrate the formation of a pre-metastatic niche (PMN), which is a critical bottleneck in metastasis. However, biomechanically oriented antitumor strategies that integrate the physicochemical interactions of tumor metastasis remain underexplored in clinical therapy. In this review, we examine the role of biomechanics in shaping the PMN and propose a two-phase model of its evolution: mechanotransductive priming and mechanical niche reconstruction. Furthermore, we clarify the role of biomechanics in tumor organotropism and the impact of anatomical differences among organs on metastasis. In conclusion, a deeper understanding of the biomechanical dimensions of the PMN may inform the development of novel biomechanical interventions to prevent and control tumor metastasis.

Keywords: Biomechanics; Organotropism; Pre-metastatic niche; Tumor metastasis

DOI: https://doi.org/10.1016/j.canlet.2025.218102

Front Cell Dev Biol. 2025 ;13 1677481

Deciphering organotropism reveals therapeutic targets in metastasis.

Jhommara Bautista, Andrés López-Cortés.

Metastasis remains the principal cause of cancer-related mortality, yet its distribution across organs is far from random. Instead, tumor cells exhibit organotropism, a consistent preference for colonizing specific distant tissues, a phenomenon shaped by anatomical constraints, molecular crosstalk, and microenvironmental compatibility. Far beyond mere mechanical entrapment in vascular beds, metastatic dissemination reflects a coordinated interplay between tumor-intrinsic programs and organ-specific niches. Tumor-derived extracellular vesicles, cytokines, and matrix-remodeling enzymes actively precondition distant sites through pre-metastatic niche formation, creating permissive microenvironments primed for colonization. Simultaneously, tissue-specific immune landscapes, stromal compositions, and mechanical architectures determine the fate of disseminated tumor cells, whether they are eliminated, enter dormancy, or form macrometastases. Phenotypic plasticity, metabolic reprogramming, and immune evasion mechanisms equip subclones with the capacity to exploit these unique niches. Across cancer types, reproducible patterns of organotropic metastasis not only guide clinical surveillance and therapeutic stratification but also reveal vulnerabilities in the metastatic cascade. This review synthesizes emerging mechanistic insights across anatomical, immunological, and molecular domains to construct a comprehensive framework of organotropism, highlighting therapeutic opportunities to intercept metastasis at organ-specific checkpoints.

Keywords: immune evasion; metabolic reprogramming; metastasis; organotropism; phenotypic plasticity; pre-metastatic niche

DOI: https://doi.org/10.3389/fcell.2025.1677481

Biomolecules. 2025 Sep 28. pii: 1376. [Epub ahead of print]15(10):

Unveiling Metabolic Signatures as Potential Biomarkers in Common Cancers: Insights from Lung, Breast, Colorectal, Liver, and Gastric Tumours.

Kha Wai Hon, Rakesh Naidu.

Reprogramming is a hallmark of cancer, enabling tumour cells to sustain rapid proliferation, resist cell death, and adapt to hostile microenvironments. This review explores the expression profiles of key metabolic enzymes and transporters involved in glucose, amino acid, and lipid metabolism across the five most deadly cancers worldwide: lung, breast, colorectal, liver, and gastric cancers. Through a comparative analysis, we identify consistent upregulation of glycolytic enzymes such as LDHA, PKM2, and HK2, as well as nutrient transporters like GLUT1, ASCT2, and LAT1, which contribute to cancer progression, metastasis, and therapy resistance. The role of enzymes involved in glutaminolysis (e.g., GLS1, GDH), one-carbon metabolism (e.g., SHMT2, PHGDH), and fatty acid synthesis (e.g., FASN, ACLY) is also examined, with emphasis on their emerging relevance as diagnostic, prognostic, and predictive biomarkers. While several metabolic proteins show strong potential for clinical translation, only a few, such as tumour M2-pyruvate kinase (TuM2-PK) and serum LDH measurement, have progressed into clinical use or trials. This review addresses some of the challenges in biomarker development. Ultimately, our findings underscore the importance of metabolic proteins not only as functional drivers of malignancy but also as promising candidates for biomarker discovery. Advancing their clinical implementation could significantly enhance early detection, treatment stratification, and personalized oncology.

Keywords: biomarker; breast cancer; colorectal cancer; gastric cancer; liver cancer; lung cancer; metabolic proteins

DOI: https://doi.org/10.3390/biom15101376