System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Review Ppublish 19 citations

PubMed: 39510293 DOI: 10.1016/j.pharmthera.2024.108742

Lessons learned from 20 years of preclinical testing in pediatric cancers.

Pharmacol Ther 264:108742

Authors: Malcolm A Smith, Peter J Houghton, Richard B Lock, John M Maris, Richard Gorlick, Raushan T Kurmasheva, Xiao-Nan Li, Beverly A Teicher, Jeffrey H Chuang, Filemon S Dela Cruz, Michael A Dyer, Andrew L Kung, Michael W Lloyd, Yael P Mossé, Timothy M Stearns, Elizabeth A Stewart, Carol J Bult, Stephen W Erickson

Affiliations

  • National Cancer Institute, Bethesda, MD, United States of America.
  • The University of Texas Health at San Antonio, TX, United States of America.
  • Children's Cancer Institute, Lowy Cancer Research Centre, School of Clinical Medicine, UNSW Medicine & Health, UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia.
  • The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States of America.
  • The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
  • Lurie Children's Hospital, Northwestern University Feiberg School of Medicine, Chicago, IL, United States of America.
  • National Cancer Institute, Bethesda, MD, United States of America.
  • The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States of America.
  • Memorial Sloan Kettering Cancer Center, New York City, NY, United States of America.
  • St. Jude Children's Research Hospital, Memphis, TN, United States of America.
  • The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, United States of America.
  • RTI International, Research Triangle Park, NC, United States of America.

Abstract

Programs for preclinical testing of targeted cancer agents in murine models of childhood cancers have been supported by the National Cancer Institute (NCI) since 2004. These programs were established to work collaboratively with industry partners to address the paucity of targeted agents for pediatric cancers compared with the large number of agents developed and approved for malignancies primarily affecting adults. The distinctive biology of pediatric cancers and the relatively small numbers of pediatric cancer patients are major challenges for pediatric oncology drug development. These factors are exacerbated by the division of cancers into multiple subtypes that are further sub-classified by their genomic properties. The imbalance between the large number of candidate agents and small patient populations requires careful prioritization of agents developed for adult cancers for clinical evaluation in children with cancer. The NCI-supported preclinical pediatric programs have published positive and negative results of efficacy testing for over 100 agents to aid the pediatric research community in identifying the most promising candidates to move forward for clinical testing in pediatric oncology. Here, we review and summarize lessons learned from two decades of experience with the design and execution of preclinical trials of antineoplastic agents in murine models of childhood cancers.

MeSH

Research Design, Antineoplastic Agents, Neoplasms, Pharmacology, Therapeutics

Cited by