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Lung cancer

Notch 3 (NOTCH3)

Cell culture and mouse studies suggest inhibiting NOTCH3 could help treat lung cancer by eliminating tumor-propagating cells (TPCs). In mice engrafted with TPCs expressing three propagation markers including Notch3, tumor burdens were elevated and survival was reduced compared with mice engrafted with cells not expressing these markers. In mice with TPCs, cisplatin increased the proportion of TPCs in tumors compared with vehicle, suggesting TPCs could be resistant to chemotherapy. In xenograft mouse models of lung cancer, small hairpin RNA−mediated knockdown of Notch3 decreased tumor burden compared with no knockdown. Next steps include understanding the molecular basis for cisplatin resistance.
OncoMed Pharmaceuticals Inc.'s OMP-59R5, an antibody to NOTCH3, is in Phase II or earlier testing to treat various cancers. At least four companies have NOTCH inhibitors in Phase I testing to treat cancer.

SciBX 6(31); doi:10.1038/scibx.2013.824
Published online Aug. 15, 2013

Patent and licensing status undisclosed

Zheng, Y. et al. Cancer Cell; published online June 8, 2013;
Contact: E. Alejandro Sweet-Cordero, Stanford University School of Medicine, Stanford, Calif.
Contact: Erica L. Jackson, Genentech Inc., South San Francisco, Calif.