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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
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SMARCA4-Directed Treatment in Oncology Clinical Trials: A Review

Sarah Hendee1, Gerald Falchook2

  • 1HCA HealthONE, Sky Ridge Medical Center, Lone Tree, CO, USA.

Journal of Immunotherapy and Precision Oncology
|June 15, 2026
PubMed

Insights

SMARCA4-directed therapies are emerging as a promising strategy for treating cancers with SMARCA4 mutations. This review summarizes ongoing clinical trials investigating these novel treatments, including small-molecule inhibitors and antibodies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • SMARCA4 is a key ATPase subunit of the SWI/SNF chromatin-remodeling complex.
  • SMARCA4 regulates gene expression via chromatin structural rearrangement.
  • SMARCA4 alterations occur in 15% of cancers with SWI/SNF complex gene mutations.

Purpose of the Study:

  • To review current SMARCA4-directed therapies in oncology clinical trials.
  • To identify emerging therapeutic strategies for SMARCA4-mutated cancers.

Main Methods:

  • Literature review of published and ongoing clinical trials.
  • Analysis of therapeutic agents targeting SMARCA4 and its pathways.

Main Results:

  • Ongoing clinical trials primarily focus on orally bioavailable small-molecule inhibitors.
  • Other investigated therapies include monoclonal antibodies and bifunctional MabPair products.
  • SMARCA4-deficient cancers may exhibit SMARCA2 upregulation, presenting a potential therapeutic target.

Conclusions:

  • SMARCA4-directed therapies represent a promising new treatment strategy for patients with SMARCA4-mutated cancers.
  • Further clinical investigation is warranted to evaluate the efficacy and safety of these novel agents.
Keywords:
SMARCA4cancerclinical trialsreview article

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