We propose harnessing p53beta via SRSF3 inhibition as a novel medical treatment of squamous cell carcinoma, a common skin cancer. Surgical excision is the current standard of care for treatment of squamous cell carcinoma; a medical treatment for this >$2 billion market would decrease patient morbidity significantly. p53 is the guardian of the genome, mutated in almost every single cancer, but is difficult to target. 

In a spontaneously regressing squamous cell carcinoma, our team found increased p53beta, a p53 isoform that causes differentiation and decreased proliferation. p53beta is regulated by SRSF3, and SRSF3 inhibition can directly increase levels of p53beta. We have shown that SRSF3 inhibition via a small molecule inhibitor of SRSF3, SFI003, leads to differentiation of keratinocytes in 2-dimensional and 3-dimensional models as well as in skin cancer cell lines. SFI003 is small enough to penetrate the skin and is a strong candidate for topical treatment of skin cancer.