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Organoids in Genetic Disorders: from Disease Modeling to Translational Applications
Stem Cell Rev Rep. 2025 Sep 11. doi: 10.1007/s12015-025-10973-x. Online ahead of print.
ABSTRACT
The emergence of organoid models has significantly bridged the gap between traditional cell cultures/animal models and authentic human disease states, particularly for genetic disorders, where their inherent genetic fidelity enables more biologically relevant research directions and enhances translational validity. This review systematically analyzes established organoid models of genetic diseases across organs (e.g., brain, eye, kidney, lung, and heart), highlighting their pivotal roles in identifying novel pathogenic genes, elucidating disease mechanisms, and advancing therapeutic strategies such as drug screening platforms, gene-editing therapies, and organ transplantation strategies. Furthermore, we critically address current limitations-including challenges in recapitulating complex pathologies and scaling production-while underscoring their potential for personalized medicine through multi-omics integration and bioengineering innovations. Although the scope of "genetic diseases" is broad, this synthesis focuses on disorders with well-defined inheritance patterns, such as monogenic disorders, copy number variations (CNVs), and aneuploidies. Despite covering only a subset of these conditions, this review aims to provide researchers with a comprehensive overview of the field, emphasizing how organoid-based approaches could accelerate both mechanistic discoveries and clinical translation in genetic disease research.
PMID:40931310 | DOI:10.1007/s12015-025-10973-x
Actin-Like Protein 6A as an Oncogene and Therapeutic Target in Cancer
Int J Med Sci. 2025 Jun 12;22(12):2906-2918. doi: 10.7150/ijms.113736. eCollection 2025.
ABSTRACT
ACTL6A, a core subunit of the SWI/SNF chromatin remodeling complex, has emerged as a critical oncogenic driver across multiple malignancies. Recent studies reveal that aberrant ACTL6A overexpression promotes tumor initiation, progression, and metastasis by orchestrating chromatin remodeling, transcriptional reprogramming, and crosstalk with key signaling pathways (e.g., Hippo/YAP, Notch, and PI3K/AKT). This review systematically synthesizes evidence from in vitro, in vivo, and clinical studies spanning hepatocellular carcinoma, breast cancer, glioblastoma, and 10 other cancer types, highlighting ACTL6A's dual role as a chromatin remodeler and an independent oncogenic effector. Key mechanisms include sustaining cancer stemness, suppressing apoptosis, enhancing DNA repair, and driving metabolic reprogramming. Clinically, ACTL6A overexpression correlates with advanced tumor stage, therapy resistance, and poor prognosis, positioning it as a promising prognostic biomarker and therapeutic target. We further discuss emerging strategies to inhibit ACTL6A (e.g., siRNA, small-molecule inhibitors) and propose combinatorial approaches to overcome drug resistance. By integrating multi-omics data and preclinical models, this review not only clarifies ACTL6A's context-dependent oncogenic networks but also bridges mechanistic insights to translational challenges, offering a roadmap for future research and therapeutic development.
PMID:40657395 | PMC:PMC12243864 | DOI:10.7150/ijms.113736