Research ArticleCancer

A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo

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Science Translational Medicine  26 Aug 2015:
Vol. 7, Issue 302, pp. 302ra136
DOI: 10.1126/scitranslmed.aac9459

Not just another Notch

Pulmonary neuroendocrine tumors, such as small cell lung cancer, are among the most difficult cancers to treat. Although standard chemotherapy regimens are available for this type of cancer, their effects are only transient, and the tumors typically acquire resistance to the drugs very quickly. Saunders et al. have discovered that DLL3, a ligand in the Notch signaling pathway, is associated with the neuroendocrine cancer phenotype. The authors targeted DLL3 with an antibody conjugated to a cytotoxic drug, which proved to be much more effective than standard chemotherapy for treating patient-derived tumor xenografts. Unlike chemotherapy, the anti-DLL3 treatment appeared to be particularly effective against tumor-initiating cells, which may account for its efficacy.

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