Research ArticleCancer

An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma

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Science Translational Medicine  13 Mar 2019:
Vol. 11, Issue 483, eaau9732
DOI: 10.1126/scitranslmed.aau9732

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No neuroblastomas left behind

Anaplastic lymphoma kinase (ALK) is frequently expressed in neuroblastoma, one of the more common pediatric cancers. Although small-molecule inhibitors of ALK are already in clinical use, the target protein often develops mutations that impede the effectiveness of these drugs. As an alternative to chemical inhibitors, Sano et al. developed an antibody-drug conjugate consisting of an antibody that recognizes ALK and a toxin that kills the ALK-expressing cells. The authors confirmed that ALK is not expressed in normal healthy tissues, indicating that this approach should be safe, and demonstrated the efficacy of the antibody-drug conjugate in mouse models of neuroblastoma with wild-type and mutant ALK.