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Many cancers resist therapeutic intervention. This is fundamentally related to intratumor heterogeneity: multiple cell populations, each with different phenotypic signatures, coexist within a tumor and its metastases. Like species in an ecosystem, cancer populations are intertwined in a complex network of ecological interactions. Most mathematical models of tumor ecology, however, cannot account for such phenotypic diversity or predict its consequences. Here, we propose that the generalized Lotka-Volterra model (GLV), a standard tool to describe species-rich ecological communities, provides a suitable framework to model the ecology of heterogeneous tumors. We develop a GLV model of tumor growth and discuss how its emerging properties provide a new understanding of the disease. We discuss potential extensions of the model and their application to phenotypic plasticity, cancer-immune interactions, and metastatic growth. Our work outlines a set of questions and a road map for further research in cancer ecology.
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http://dx.doi.org/10.1016/j.isci.2024.110699 | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
J Clin Invest
September 2025
Department of Cellular and Molecular Medicine, UCSD, La Jolla, United States of America.
3-O-sulfation of heparan sulfate (HS) is the key determinant for binding and activation of Antithrombin III (AT). This interaction is the basis of heparin treatment to prevent thrombotic events and excess coagulation. Antithrombin-binding HS (HSAT) is expressed in human tissues, but is thought to be expressed in the subendothelial space, mast cells, and follicular fluid.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Biochemical Pathophysiology, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Adrenal lipomas are benign tumors containing ectopic adipose tissue in the adrenal gland, an organ that normally lacks both adipocytes and their progenitors. The origin of this ectopic fat remains enigmatic, and the absence of a genetic animal model has hindered its investigation. Phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P], a key signaling lipid that regulates cellular growth and differentiation, is tightly regulated by the lipid phosphatases PTEN (phosphatase and tensin homolog) and SHIP2 (SH2-containing inositol phosphatase 2).
View Article and Find Full Text PDFJ Neurooncol
September 2025
Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China.
Rationale And Objectives: Double expression lymphoma (DEL) is an independent high-risk prognostic factor for primary CNS lymphoma (PCNSL), and its diagnosis currently relies on invasive methods. This study first integrates radiomics and habitat radiomics features to enhance preoperative DEL status prediction models via intratumoral heterogeneity analysis.
Materials And Methods: Clinical, pathological, and MRI imaging data of 139 PCNSL patients from two independent centers were collected.
J Neurooncol
September 2025
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Purpose: NOTCH3 is increasingly implicated for its oncogenic role in many malignancies, including meningiomas. While prior work has linked NOTCH3 expression to higher-grade meningiomas and treatment resistance, the metabolic phenotype of NOTCH3 activation remains unexplored in meningioma.
Methods: We performed single-cell RNA sequencing on NOTCH3 + human meningioma cell lines.