SRC-3 Regulation of regulatory T cell (Treg) function
Using an aggressive E0771 mouse breast cell line syngeneic immune-intact murine model, here we show that breast tumors were ‘permanently eradicated’ in a genetically engineered tamoxifen-inducible Treg-cell specific SRC-3 knockout (KO) female mouse that does not possess a systemic autoimmune pathological phenotype. Importantly, a single adoptive transfer of SRC-3 KO Tregs can completely abolish pre-established breast tumors by generating potent antitumor immunity with a durable effect that prevents tumor reoccurrence.Proc Natl Acad Sci, 2023
Sang Jun Han, Prashi Jain, Yosef Gilad, Yan Xia, Nuri Sung, Mi Jin Park, Adam M. Dean, Rainer B. Lanz, Jianming Xu, Clifford C. Dacso1, David M. Lonard, and Bert W. O’Malley See paper
Finds that steroid receptor coactivator stimulation with MCB-10-1 is a potential therapeutic strategy for reducing inflammation and oxidative damage that cause neurologic impairment following an acute ischemic stroke.
Front Mol Neurosci, 2022
McClendon LK, Garcia RL, Lazaro T, Robledo A, Vasandani V, Luna ZAE, Rao AS, Srivatsan A, Lonard DM, Dacso CC, Kan P, O’Malley BW. A steroid receptor coactivator small molecule “stimulator” attenuates post-stroke ischemic brain injury. Front Mol Neurosci. 2022 Dec 1;15:1055295. doi:10.3389/fnmol.2022.1055295. PMID: 36533127; PMCID: PMC9751323.
Describes a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs.
Scientific Reports, 2021
Nikolai BC, Jain P, Cardenas DL, York B, Feng Q, McKenna NJ, Dasgupta S, Lonard DM, O’Malley BW. Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs. Sci Rep. 2021;11(1):3441. doi: 10.1038/s41598-021-82945-3. PMID: 33564037; PMCID: PMC7873281.
SRC-3 small molecule stimulators
Steroid receptor coactivator stimulation with MCB-10-1 is a potential therapeutic strategy for reducing inflammation and oxidative damage that cause neurologic impairment following an acute ischemic stroke.Front Mol Neurosci, 2022
Han SJ, Sung N, Wang J, O’Malley BW, Lonard DM. Steroid receptor coactivator-3 inhibition generates breast cancer antitumor immune microenvironment. Breast Cancer Res. 2022;24:73. doi: 10.1186/s13058-022-01568-2. PMID: 36316775; PMCID: PMC9620627.
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In this paper, we show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function.
Proc Natl Acad Sci, 2020
Mullany LK, Rohira AD, Leach JP, Kim JH, Monroe TO, Ortiz AR, Stork B, Gaber MW, Sarkar P, Sikora AG, Rosengart TK, York B, Song Y, Dacso CC, Lonard DM, Martin JF, O’Malley BW. A steroid receptor coactivator stimulator (MCB-613) attenuates adverse remodeling after myocardial infarction. Proc Natl Acad Sci USA. 2020;117(49):31353-31364. doi: 10.1073/pnas.2011614117. Epub 2020 Nov 23. PMID: 33229578; PMCID: PMC7733826.
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This paper demonstrates that inhibition of SRC-3 with a small molecule inhibitor can significantly inhibit pancreatic adenocarcinoma tumor growth in orthotopic pancreatic cancer mouse models. Combined with other data, this study establishes SRC-3 as a promising therapeutic target for pancreatic cancer treatment.
Cancer Lett. 2019
Xianzhou Song, Hui Chen, Chengwei Zhang, Yang Yu, Zhongyuan Chen, Han Liang, George Van Buren II, Amy L. McElhany, William E. Fisher, David M. Lonard, Bert W. O’Malley, and Jin Wang.