Opportunities and Challenges in Drug Development for Pediatric Cancers

Cancer Discov. 2021 Mar;11(3):545-559. doi: 10.1158/2159-8290.CD-20-0779. Epub 2020 Dec 4.

Abstract

The use of targeted small-molecule therapeutics and immunotherapeutics has been limited to date in pediatric oncology. Recently, the number of pediatric approvals has risen, and regulatory initiatives in the United States and Europe have aimed to increase the study of novel anticancer therapies in children. Challenges of drug development in children include the rarity of individual cancer diagnoses and the high prevalence of difficult-to-drug targets, including transcription factors and epigenetic regulators. Ongoing pediatric adaptation of biomarker-driven trial designs and further exploration of agents targeting non-kinase drivers constitute high-priority objectives for future pediatric oncology drug development. SIGNIFICANCE: Increasing attention to drug development for children with cancer by regulators and pharmaceutical companies holds the promise of accelerating the availability of new therapies for children with cancer, potentially improving survival and decreasing the acute and chronic toxicities of therapy. However, unique approaches are necessary to study novel therapies in children that take into account low patient numbers, the pediatric cancer genomic landscape and tumor microenvironment, and the need for pediatric formulations. It is also critical to evaluate the potential for unique toxicities in growing hosts without affecting the pace of discovery for children with these life-threatening diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor
  • Child
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Disease Susceptibility
  • Drug Development* / legislation & jurisprudence
  • Drug Development* / methods
  • Drug Evaluation, Preclinical
  • Drug and Narcotic Control
  • Genomics / methods
  • Humans
  • Molecular Targeted Therapy / adverse effects
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / etiology
  • Pediatrics
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor