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William J. Gradishar, MD, FACP, FASCO


AACR 2024: Novel Compounds May Target MIEN1 Pathway to Treat Breast Cancer

By: Celeste L. Dixon
Posted: Wednesday, April 17, 2024

First-in-class molecules that target the migration and invasion enhancer 1 (MIEN1) signaling pathway—a pathway potentially significant in the development of breast cancer—have been identified and completely characterized, according to a two-person research team. Amit Kumar Tripathi, PhD, and Jamboor K. Vishwanatha, PhD, both of the University of North Texas Health Science Center, Fort Worth, leveraged conserved prenylation motifs and the immunoreceptor tyrosine-based activation motif within MIEN1 to pinpoint anticancer peptides. They presented their work during the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract LB034/16). MIEN1 overexpression characterizes several cancers, including breast cancer, and it facilitates cancer cell migration and invasion.

This is the first report of short peptides that are based on the MIEN1 protein sequence that can inhibit cancer signaling pathways, effectively impeding cancer progression both in vitro and in vivo, the investigators asserted. Among the bioactive peptides they identified were LA3IK and RP-7. Additionally, noted the duo, the peptides effectively inhibited genes and proteins that drive cancer cell migration, invasion, and epithelial-mesenchymal transition pathways. Concurrently, peptides “suppress[ed] EGF-induced NF-kB nuclear translocation in metastatic breast cancer cells.”

Of note, said Drs. Tripathi and Vishwanatha, “mice tolerated high peptide doses of up to 90 mg/kg well, surpassing significantly lower doses of 5 mg/kg intravenously and 30 mg/kg intraperitoneally used in both in vivo pharmacokinetic studies and orthotopic mouse model assays.” Further, “D-isomers of LA3IK and RP-7 showed enhanced anticancer activity compared with their L-isomers, and D-LA3IK remained stable in mouse plasma for 24 hours with 75% remaining, exhibiting superior pharmacokinetic properties over D/L–RP-7.”

Disclosure: The study authors reported no conflicts of interest.

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