NIH R01 · 2025
Modulation of Mcl-1 for Treatment of Lung Cancer
Summary KRAS mutations activate Raf/MEK/ERK1/2 that can directly phosphorylate Mcl-1 at T163, enhancing Mcl-1’s function. KRAS mutations also activate PI3K/AKT that can inactivate GSK-3 and inhibit GSK-3-mediated pMcl-1 at S159 to reduce Mcl-1 degradation. We hypothesize that KRAS mutation-activated ERK1/2 and PI3K/AKT pathways contribute to stabilization of Mcl-1 via upregulation of pMcl-1 at T163 and downregulation of pMcl-1 at S159 in lung cancer. Our preliminary data show increased pMcl-1 at T163 in tumor tissues from NSCLC patients, which associated with worse survival outcome, suggesting that pMcl-1 at T163 may provide a new therapeutic target and a prognostic biomarker in NSCLC…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.