Chin Med J Pulm Crit Care Med. 2026 Jun 6;4(2):99-116. doi: 10.1016/j.pccm.2026.05.005. eCollection 2026 Jun.

ABSTRACT

Lung diseases-including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, interstitial lung diseases (ILDs), and rare conditions like cystic fibrosis-remain major drivers of global morbidity and mortality. Timely diagnosis and individualized treatment are frequently challenged by heterogeneous clinical phenotypes and the complexity of multimodal data. This review provides a critical synthesis of the transformative role of artificial intelligence (AI) in respiratory care, tracing the paradigm shift from classical machine learning to emerging large language models (LLMs) and multimodal foundation models. We evaluate the performance of AI across the patient care continuum: beginning with radiologist-level nodule detection and automated diagnostics, advancing into AI-powered clinical decision support systems (CDSS) and surgical/radiotherapeutic interventions, and culminating in prognostic modeling and "digital twin" simulations for longitudinal patient management. Furthermore, we explore the translational frontier of precision medicine, examining how AI leverages multi-omics and liquid biopsies to drive novel biomarker discovery and accelerate drug repurposing. Finally, we address persistent sociotechnical barriers-including data sovereignty, legal liability, and the critical need for prospective clinical validation-proposing a translational roadmap for the safe integration of generalist medical AI into clinical workflows.

PMID:42396189 | PMC:PMC13323542 | DOI:10.1016/j.pccm.2026.05.005

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839