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

ABSTRACT: 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.

SUBMITTER: Southgate HED

PROVIDER: S-EPMC7145987 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Southgate Harriet E D HED Chen Lindi L Curtin Nicola J NJ Tweddle Deborah A DA

Frontiers in oncology 20200403

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 de ...[more]

PMID: 32309213

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