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SMARCA4-Deficient Undifferentiated Thoracic Tumor: Clinical Features and Prognosis of a Case Series and Literature

Fangzhen Shan1, Shuntao Liang2, Youwen Zhang3

  • 1Medical Research Center, Affiliated Hospital of Jining Medical University, Shandong, China.

The Clinical Respiratory Journal
|January 23, 2026
PubMed
Abstract

Insights

Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are aggressive neoplasms. Immunotherapy and targeted agents show promise for managing SMARCA4-UT, suggesting new therapeutic avenues.

Area of Science:

  • Oncology
  • Genetics
  • Pathology

Background:

  • Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are rare, aggressive epithelioid neoplasms.
  • These tumors are characterized by SMARCA4 gene loss and typically diagnosed at advanced stages with poor prognosis.
  • Current treatment lacks standardized protocols and approved targeted therapies.

Purpose of the Study:

  • To present a case series of nine patients with thoracic SMARCA4-UT.
  • To detail demographic, pathological, imaging, and treatment data for these patients.
  • To conduct a literature review and genomic analysis of SMARCA4 mutations in lung cancer.

Main Methods:

  • Case series of nine patients with thoracic SMARCA4-UT.
  • Comprehensive literature review.
  • Genomic analysis of SMARCA4 mutations in lung cancer.

Main Results:

  • The cohort consisted of predominantly male smokers (mean age 63 years).
  • All cases showed loss of BRG1 expression, negative for TTF-1 and p40, with preserved SMARCB1/INI-1.
  • Patients responded poorly to chemotherapy but showed partial response to immunotherapy or targeted agents. SMARCA4 mutations are linked to poorer lung cancer prognosis.

Conclusions:

  • Immunotherapy and targeted therapies demonstrate potential for managing thoracic SMARCA4-UT.
  • Further investigation into these treatment modalities is warranted.
  • Exploring the tumor's genetic and molecular landscape may reveal novel therapeutic targets.
Keywords:
Brahma‐related gene 1SMARCA4immunotherapythoracic tumorundifferentiated tumor

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