Research ArticleCancer

Delta-like protein 3 expression and therapeutic targeting in neuroendocrine prostate cancer

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Science Translational Medicine  20 Mar 2019:
Vol. 11, Issue 484, eaav0891
DOI: 10.1126/scitranslmed.aav0891

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Lessons from one tumor help with another

Neuroendocrine prostate cancer is an aggressive tumor subtype that can arise late in the course of the disease and drive therapeutic resistance. Puca et al. demonstrate the feasibility of targeting it with an antibody-drug conjugate against delta-like protein 3 (DLL3), a recently identified therapeutic being tested in small cell lung cancer, another aggressive neuroendocrine tumor. The authors confirmed the presence of DLL3 in most neuroendocrine prostate cancers, but not in localized tumors or normal prostate, and showed its association with aggressive clinical features. They then demonstrated the effectiveness of targeting DLL3 in multiple mouse models as well as a human patient.

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