SMARCA4-Directed Treatment in Oncology Clinical Trials: A Review.

SMARCA4 is an ATPase subunit in the switch/sucrose non-fermentable complex (SWI/SNF), a chromatin-remodeling complex. SMARCA4 provides energy for the SWI/SNF complex to regulate gene expression through chromatin structural rearrangement and transcription regulation. In SMARCA4-deficient cancers, its paralog SMARCA2 is sometimes upregulated and can serve as a pharmacological target. Of the 20-25% of cancers identified to have a mutation in a gene encoding a protein for the SWI/SNF complex, 15% of these alterations include SMARCA4 alterations. Therefore, SMARCA4-directed therapies are under investigation in clinical trials and are a promising new strategy for treating patients with a SMARCA4-mutated cancer. Currently, all published clinical trials of SMARCA4-directed therapies are for orally bioavailable small-molecule inhibitors. Clinical trials without results include small-molecule inhibitors, monoclonal antibodies, and a bifunctional MabPair product. The aim of this literature review was to summarize the current SMARCA4-directed therapies in oncology clinical trials.