
The PI3K-mTOR pathway is crucial in breast cancer development and resistance to targeted therapies. To better understand the role of specific mTOR complexes, researchers utilized RMC-6272, a molecule that selectively impairs mTORC1 over mTORC2. Inhibition of mTORC1 by RMC-6272 induced apoptosis in ER+/HER2- breast cancer cells, particularly those with PIK3CA or PTEN mutations, by targeting the 4EBP1 protein and reducing MCL1, a pro-survival protein. RMC-6272 also inhibited key oncogenic pathways and showed greater efficacy than the partial mTORC1 inhibitor everolimus. It remained effective in hormone therapy-resistant cells and patient-derived xenografts, including those resistant to CDK4/6 inhibitors. These findings suggest that bi-steric mTORC1-selective inhibition could overcome therapy resistance in ER+ breast cancers.
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