Treatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go

Int J Mol Sci. 2024 Mar 13;25(6):3237. doi: 10.3390/ijms25063237.


Recently, the fifth edition of the WHO classification recognized the thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with SMARCA4 deficiency because of the different clinicopathological characteristics of these two diseases. SMARCA4-UT mainly occurs in young to middle-aged adults and involves a large mass compressing the tissues surrounding the mediastinum and lung parenchyma. Unfortunately, SMARCA4-UT shows a high probability of recurrence after upfront surgery as well as radiotherapy resistance; moreover, chemotherapy has low efficacy. Moreover, given the recent classification of SMARCA4-UT, no data concerning specific clinical trials are currently available. However, several case reports show immunotherapy efficacy in patients with this disease not only in a metastatic setting but also in a neoadjuvant manner, supporting the development of clinical trials. In addition, preclinical data and initial clinical experiences suggest that inhibiting pathways such as CDK4/6, AURKA, ATR, and EZH2 may be a promising therapeutic approach to SMARCA4-UT.

Keywords: SMARCA4-UT; clinicopathological features; immunotherapy.

Publication types

  • Review

MeSH terms

  • Adult
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • DNA Helicases / genetics
  • Humans
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics
  • Sarcoma* / pathology
  • Transcription Factors / genetics


  • Biomarkers, Tumor
  • SMARCA4 protein, human
  • DNA Helicases
  • Nuclear Proteins
  • Transcription Factors