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A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program

Leukemia volume 30, pages 2133–2141 (2016)Cite this article

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Abstract

Acute lymphoblastic leukemia (ALL) in children exemplifies how multi-agent chemotherapy has improved the outcome for patients. Refinements in treatment protocols and improvements in supportive care for this most common pediatric malignancy have led to a cure rate that now approaches 90%. However, certain pediatric ALL subgroups remain relatively intractable to treatment and many patients who relapse face a similarly dismal outcome. Moreover, survivors of pediatric ALL suffer the long-term sequelae of their intensive treatment throughout their lives. Therefore, the development of drugs to treat relapsed/refractory pediatric ALL, as well as those that more specifically target leukemia cells, remains a high priority. As pediatric malignancies represent a minority of the overall cancer burden, it is not surprising that they are generally underrepresented in drug development efforts. The identification of novel therapies relies largely on the reappropriation of drugs developed for adult malignancies. However, despite the large number of experimental agents available, clinical evaluation of novel drugs for pediatric ALL is hindered by limited patient numbers and the availability of effective established drugs. The Pediatric Preclinical Testing Program (PPTP) was established in 2005 to provide a mechanism by which novel therapeutics could be evaluated against xenograft and cell line models of the most common childhood malignancies, including ALL, to prioritize those with the greatest activity for clinical evaluation. In this article, we review the results of >50 novel agents and combinations tested against the PPTP ALL xenografts, highlighting comparisons between PPTP results and clinical data where possible.

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Acknowledgements

This research was funded by grants from the National Cancer Institute (NOI-CM-42216 and NOI-CM-91001-03). We acknowledge the numerous researchers who provided technical assistance and data analysis over the course of this project. Children’s Cancer Institute is affiliated with the University of New South Wales and The Sydney Children’s Hospitals Network.

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Authors and Affiliations

  1. Leukaemia Biology Program, Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, New South Wales, Australia

    L Jones, H Carol, K Evans, J Richmond & R B Lock

  2. Molecular Medicine, Greehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    P J Houghton

  3. Cancer Therapy Evaluation Program, NCI, Bethesda, MD, USA

    M A Smith

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  1. L Jones
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  2. H Carol
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  3. K Evans
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Correspondence to R B Lock.

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Jones, L., Carol, H., Evans, K. et al. A review of new agents evaluated against pediatric acute lymphoblastic leukemia by the Pediatric Preclinical Testing Program. Leukemia 30, 2133–2141 (2016). https://doi.org/10.1038/leu.2016.192

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  • DOI: https://doi.org/10.1038/leu.2016.192

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