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

MedComm (2020). 2025 Jul 11;6(7):e70292. doi: 10.1002/mco2.70292. eCollection 2025 Jul.

ABSTRACT

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinical translation. This review systematically categorizes CAF subtypes by origin, biomarkers, and TME-specific functions, focusing on their roles in chemoresistance, maintenance of stemness, and formation of immunosuppressive niches. We evaluate emerging targeting approaches, including selective depletion of tumor-promoting subsets (e.g., fibroblast activation protein+ CAFs), epigenetic reprogramming toward antitumor phenotypes, and inhibition of CXCL12/CXCR4 or transforming growth factor-beta signaling pathways. Spatial multiomics-driven combinatorial therapies, such as the synergistic use of CAFs and immune checkpoint inhibitors, are highlighted as strategies to overcome microenvironment-driven resistance. By integrating CAF biology with translational advances, this work provides a roadmap for developing subtype-specific biomarkers and precision stromal therapies, directly informing efforts to disrupt tumor-stroma coevolution. Key concepts include spatial transcriptomics, stromal reprogramming, and tumor-stroma coevolution, offering actionable insights for both mechanistic research and clinical innovation.

PMID:40656546 | PMC:PMC12246558 | DOI:10.1002/mco2.70292