Key Points
• Source: Cancers
• Conclusion/Relevance: “In summary, the combination of MSU42011 plus anti-PD1 or anti-PDL1 antibodies was efficacious in reducing tumor number, tumor size, and burden in the A/J mouse model of Kras-driven of lung cancer. Additionally, these combinations led to an increase in cytotoxic CD8 T cells with an increased capability to produce IFNγ.”
• Retinoid X receptors (RXRs) belong to the nuclear receptor superfamily and after ligand binding, function as transcription factors to influence various cell functions.
• In the current study, researchers assessed MSU42011, which is a novel RXR receptor activator. This agent decreased the tumor burden in immunocompetent mouse models of HER2-positive breast cancer and Kras-driven lung cancer. The tumor microenvironment consists of numerous immune cells, which are able to block or promote tumor growth.
• MSU42011 influenced T cells within the tumor, thus decreasing tumor-promoting immune cells and increasing tumor-killing cells. Furthermore, MSU42011 plus immunotherapy (anti-PDL1 and anti-PD1 antibodies) lowered tumor burden vs individual treatments in the lung cancer model.
• The targeting of KRAS or downstream effectors, including p-ERK, has been an area of high research interest, with recent progress made with MAPK inhibitors and KRAS G12C inhibitors. “However, these inhibitors are toxic, ineffective against other Kras mutations (such as the Q61L mutation found in the A/J lung cancer model or the predominant G12D mutation found in pancreatic cancer), or have not been explored in the context of the tumor microenvironment [78]. The data reported here are encouraging since the RXR agonist MSU42011 not only decreased the expression of p-ERK and tumor-promoting immune populations but also simultaneously increased tumor-suppressive immune populations,” wrote the authors.