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Targeting the DNA Damage Response for the Treatment of High Risk Neuroblastoma

Lookup NU author(s): Harriet Southgate, Dr Lindi Chen, Professor Nicola CurtinORCiD, Professor Deborah Tweddle


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© Copyright © 2020 Southgate, Chen, Curtin and Tweddle.Despite intensive multimodal therapy, the survival rate for high risk neuroblastoma (HR-NB) remains <50%. Most cases initially respond to treatment but almost half will subsequently relapse with aggressive treatment resistant disease. Novel treatments exploiting the molecular pathology of NB and/or overcoming resistance to current genotoxic therapies are needed before survival rates can significantly improve. DNA damage response (DDR) defects are frequently observed in HR-NB including allelic deletion and loss of function mutations in key DDR genes, oncogene induced replication stress and cell cycle checkpoint dysfunction. Exploiting defects in the DDR has been a successful treatment strategy in some adult cancers. Here we review the genetic features of HR-NB which lead to DDR defects and the emerging molecular targeting agents to exploit them.

Publication metadata

Author(s): Southgate HED, Chen L, Curtin NJ, Tweddle DA

Publication type: Review

Publication status: Published

Journal: Frontiers in Oncology

Year: 2020

Volume: 10

Online publication date: 03/04/2020

Acceptance date: 03/03/2020

ISSN (electronic): 2234-943X

Publisher: Frontiers Media S.A.


DOI: 10.3389/fonc.2020.00371