Editors' ChoiceCancer

Not just another Notch

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Sci. Signal.  01 Sep 2015:
Vol. 8, Issue 392, pp. ec252
DOI: 10.1126/scisignal.aad3208

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, the tumors typically acquire resistance to the drugs. Saunders et al. 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 was more effective than standard chemotherapy for treating patient-derived tumor xenografts in mice. Unlike chemotherapy, the anti-DLL3 treatment appeared particularly effective against tumor-initiating cells, which may account for its efficacy.

L. R. Saunders, A. J. Bankovich, W. C. Anderson, M. A. Aujay, S. Bheddah, K. Black, R. Desai, P. A. Escarpe, J. Hampl, A. Laysang, D. Liu, J. Lopez-Molina, M. Milton, A. Park, M. A. Pysz, H. Shao, B. Slingerland, M. Torgov, S. A. Williams, O. Foord, P. Howard, J. Jassem, A. Badzio, P. Czapiewski, D. H. Harpole, A. Dowlati, P. P. Massion, W. D. Travis, M. C. Pietanza, J. T. Poirier, C. M. Rudin, R. A. Stull, S. J. Dylla, A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci. Transl. Med. 7, 302ra136 (2015). [Abstract]