Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports

Abstract 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 sup...

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Main Authors: Liwen Wang, Hua Ke, Chengdi Wang, Ke Wang
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
Subjects:
Online Access:https://doi.org/10.1007/s12672-025-03060-7
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author Liwen Wang
Hua Ke
Chengdi Wang
Ke Wang
author_facet Liwen Wang
Hua Ke
Chengdi Wang
Ke Wang
author_sort Liwen Wang
collection DOAJ
description Abstract 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. SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) represents a particularly aggressive subtype associated with dismal clinical outcomes. The reported overall survival (OS) for patients with SMARCA4-dNSCLC is only 2–3 months. In addition, chemotherapy has shown limited efficacy against this subtype and an effective treatment for SMARCA4-dNSCLC has not yet been established. Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of advanced NSCLC, little is known about their efficacy in SMARCA4-dNSCLC. In this report, we present two cases of SMARCA4-dNSCLC patients who achieved remarkable clinical benefits following ICI treatment, with prolonged progression-free survival (PFS). These findings suggest that ICI-based immunotherapy combined with chemotherapy might be a promising therapy for SMARCA4-dNSCLC and may warrant early implementation following diagnosis to potentially prolong patient survival.
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publishDate 2025-07-01
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series Discover Oncology
spelling doaj-art-6ff47366f423495cbf33cb005c53db612025-08-20T03:38:15ZengSpringerDiscover Oncology2730-60112025-07-011611710.1007/s12672-025-03060-7Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reportsLiwen Wang0Hua Ke1Chengdi Wang2Ke Wang3Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan UniversityDepartment of Respiratory Medicine, Chengdu Seventh People’s HospitalDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Targeted Tracer Research and Development Laboratory, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, West China School of Medicine, Sichuan UniversityDepartment of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan UniversityAbstract 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. SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) represents a particularly aggressive subtype associated with dismal clinical outcomes. The reported overall survival (OS) for patients with SMARCA4-dNSCLC is only 2–3 months. In addition, chemotherapy has shown limited efficacy against this subtype and an effective treatment for SMARCA4-dNSCLC has not yet been established. Although immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of advanced NSCLC, little is known about their efficacy in SMARCA4-dNSCLC. In this report, we present two cases of SMARCA4-dNSCLC patients who achieved remarkable clinical benefits following ICI treatment, with prolonged progression-free survival (PFS). These findings suggest that ICI-based immunotherapy combined with chemotherapy might be a promising therapy for SMARCA4-dNSCLC and may warrant early implementation following diagnosis to potentially prolong patient survival.https://doi.org/10.1007/s12672-025-03060-7SMARCA4Non-small cell lung carcinomaImmune checkpoint inhibitorSintilimabChemotherapy
spellingShingle Liwen Wang
Hua Ke
Chengdi Wang
Ke Wang
Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports
Discover Oncology
SMARCA4
Non-small cell lung carcinoma
Immune checkpoint inhibitor
Sintilimab
Chemotherapy
title Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports
title_full Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports
title_fullStr Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports
title_full_unstemmed Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports
title_short Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports
title_sort successful treatment with sintilimab for smarca4 deficient non small cell lung carcinoma two case reports
topic SMARCA4
Non-small cell lung carcinoma
Immune checkpoint inhibitor
Sintilimab
Chemotherapy
url https://doi.org/10.1007/s12672-025-03060-7
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AT chengdiwang successfultreatmentwithsintilimabforsmarca4deficientnonsmallcelllungcarcinomatwocasereports
AT kewang successfultreatmentwithsintilimabforsmarca4deficientnonsmallcelllungcarcinomatwocasereports