Chromosome 11q loss and MYCN amplification demonstrate synthetic lethality with checkpoint kinase 1 inhibition in neuroblastoma.

Autor:	Keller KM; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Eleveld TF; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Schild L; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., van den Handel K; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., van den Boogaard M; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Amo-Addae V; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Eising S; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Ober K; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Koopmans B; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Looijenga L; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Tytgat GAM; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands., Ylstra B; Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands., Molenaar JJ; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.; Department of Pharmaceutical Sciences, University Utrecht, Utrecht, Netherlands., Dolman MEM; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.; Children's Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, NSW, Australia.; School of Women's and Children's Health, Faculty of Medicine, UNSW Sydney, Kensington, NSW, Australia., van Hooff SR; Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2022 Sep 27; Vol. 12, pp. 929123. Date of Electronic Publication: 2022 Sep 27 (Print Publication: 2022).
DOI:	10.3389/fonc.2022.929123
Abstrakt:	Neuroblastoma is the most common extracranial solid tumor found in children and despite intense multi-modal therapeutic approaches, low overall survival rates of high-risk patients persist. Tumors with heterozygous loss of chromosome 11q and MYCN amplification are two genetically distinct subsets of neuroblastoma that are associated with poor patient outcome. Using an isogenic 11q deleted model system and high-throughput drug screening, we identify checkpoint kinase 1 (CHK1) as a potential therapeutic target for 11q deleted neuroblastoma. Further investigation reveals MYCN amplification as a possible additional biomarker for CHK1 inhibition, independent of 11q loss. Overall, our study highlights the potential power of studying chromosomal aberrations to guide preclinical development of novel drug targets and combinations. Additionally, our study builds on the growing evidence that DNA damage repair and replication stress response pathways offer therapeutic vulnerabilities for the treatment of neuroblastoma. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Keller, Eleveld, Schild, van den Handel, van den Boogaard, Amo-Addae, Eising, Ober, Koopmans, Looijenga, Tytgat, Ylstra, Molenaar, Dolman and van Hooff.)
Databáze:	MEDLINE
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