Research ArticleCancer

Therapeutic targeting of PGBD5-induced DNA repair dependency in pediatric solid tumors

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Science Translational Medicine  01 Nov 2017:
Vol. 9, Issue 414, eaam9078
DOI: 10.1126/scitranslmed.aam9078

Synthetic lethality, pediatric edition

Although a variety of therapeutic regimens are available for pediatric solid tumors, they are often ineffective and typically nonspecific. Henssen et al. determined that expression of a DNA transposase called PGBD5 is common in these tumors and presents a therapeutic vulnerability. The authors demonstrated that cells expressing PGBD5 are dependent on DNA repair through nonhomologous end joining, then identified a drug that inhibits this DNA repair pathway and is therefore active against many pediatric tumor types, particularly when combined with chemotherapy, while sparing surrounding nontumor tissues.

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