Bardees Foda

Abstract Aim: Overcoming therapy resistance is critical for effective melanoma control. Upregulation of Rho/MRTF signaling in human and mouse melanomas causes resistance to targeted therapies. Inhibition of this pathway by MRTFi, CCG-257081 resensitized resistant melanomas to BRAF and MEK inhibitors. It also prevented the development of resistance to vemurafenib (Vem). Here, we investigate the role of apoptosis and the protein pirin in CCG-257081-mediated suppression of drug resistance.

1. Introduction Despite effective treatments for melanoma, drug resistance, both intrinsic and acquired, limits durable cures [1,2]. Growth of mutant BRAFV600E/K melanoma tumors is sustained by constitutive activity of the MAPK pathway, and tumor growth is inhibited by targeted therapies such as vemurafenib, trametinib, and dabrafenib, but resistance inevitably develops. Similarly for immunotherapies, including anti-PDL1, anti-PD1, or anti-CTLA4 [3], intrinsic or acquired resistance is problematic.

Ashley E. Ciecko, David M. Schauder, Bardees Foda, Galina Petrova, Moujtaba Y. Kasmani, Robert Burns, Chien-Wei Lin, William R. Drobyski, Weiguo Cui and Yi-Guang Chen J Immunol October 15, 2021, 207 (8) 1990-2004; DOI: https://doi.org/10.4049/jimmunol.2100362 Key Points Functionally distinct subsets of CD8 T cells infiltrate islets in type 1 diabetes. Self-renewing islet CD44highTCF1+ CD8 T cells maintain the autoreactive response.