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SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) typically lacks target-driven gene alterations and are primarily resistant to cytotoxic drugs. There is currently no standard treatment, especially for those who are unwilling or unable to receive chemotherapy. This case reported that chemotherapy-free strategy with tislelizumab and fruquintinib was utilized as a first-line treatment for a patient with SMARCA4-deficient NSCLC, and the patient achieved remarkable partial remission and lasted more than two years of disease control without severe adverse events.
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http://dx.doi.org/10.3389/fimmu.2025.1521828 | DOI Listing |
Nat Commun
September 2025
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Ferroptosis, an iron-dependent form of cell death, holds promise for cancer therapy. However, the intricate link between ferroptosis and oncogenic mutations remains unclear. Here we show that SMARCA4, a well-established tumour suppressor whose deficiency is associated with poor prognosis and resistance to treatments, sensitizes non-small cell lung cancer (NSCLC) cells to ferroptosis.
View Article and Find Full Text PDFOncologist
August 2025
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Background: SMARCA4-deficient thoracic tumors (SDTTs) mainly include SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-dUT) and SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC). Comparative studies between these subtypes remain limited, and no standardized therapeutic guidelines have been established.
Materials And Methods: This study retrospectively analyzed 102 patients with SDTT from January 2020 to May 2024.
Lung Cancer
August 2025
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston MA 02115, USA. Electronic address:
Introduction: SMARCA4 inactivation occurs in a subset of non-small cell lung carcinomas (NSCLC) and undifferentiated thoracic tumors, typically as an early clonal alteration in smokers. While rarely observed as an acquired event, the frequency and significance remain unclear. Given the aggressive nature of SMARCA4-deficient thoracic tumors, we hypothesized that SMARCA4 inactivation could represent a mechanism of progression and resistance following therapy.
View Article and Find Full Text PDFDiscov Oncol
July 2025
Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
SMARCA4, one of the subunits of the switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex, plays a pivotal role in transcriptional regulation. By disrupting histone-DNA contacts, this complex modulates gene expression patterns, and accumulating evidence suggests its tumor suppressor function. Inactivating mutations and loss of SMARCA4 expression have been shown in various tumors, with approximately 8% of non-small cell lung carcinomas (NSCLCs) harboring such alternations.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
June 2025
Department of Nuclear Medicine, The First Affiliated Hospital of Guilin Medical University, Le Qun Road No.15, XiuFeng District, Guilin, 541000, Guangxi, China.
Purpose: This study aims to characterize SMARCA4-deficient tumors using F-FDG PET/CT and explore its role in diagnosis, staging, therapeutic response assessment, and prognosis across multiple pathological subtypes.
Methods: We retrospectively analyzed four patients with histologically confirmed SMARCA4-deficient tumors. Clinical features, F-FDG PET/CT findings, pathological subtypes, molecular characteristics, treatment modalities, and outcomes were evaluated.