With its aggressive aggressiveness and resistance to standard treatments, pancreatic ductal adenocarcinoma (PDAC) offers a major obstacle in oncology. Researchers looking for creative therapies are investigating the possibilities of Stimulator of Interferon Genes (STING) agonists, meant to trigger the natural immune response against malignancies. The researchers looked at possible combo treatments that boost the impact of STING agonists such as systemically given molecule diABZI. After screening 430 kinase inhibitors, they found MEK inhibitors as main synergistic agents driving tumor cell death. Especially in CFPAC-1 cells, which showed strong STING expression levels, this synergy was most evident. The research showed that MEK inhibition not only enhanced the capacity of STING agonism to trigger type I interferon-dependent cell death but also produced notable in vivo tumor regression. This study emphasizes the need of knowing the processes behind STING-mediated effects, therefore enabling more successful combination treatments for PDAC.
Figure 1. The researchers utilized CFPAC-1 and SUIT2 cells with CRISPR/Cas9-mediated deletion of the IFNα receptor 1 (IFNAR1-KO) to assess the role of Type I IFN signaling in the synergy between STING activation and MEK inhibition. (Ghukasyan R, et al., 2023)
Creative Biogene's Cas9 Stable Cell Line - CFPAC-1 offers a robust platform for such investigations. The design incorporates multiple guide RNAs targeting key genes related to STING signaling and tumor biology. Following electroporation, the CFPAC-1 cells demonstrated high knockout efficiency, allowing for precise gene editing and functional studies.