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Developmental origins and emerging therapeutic opportunities for childhood cancer

Mariella Filbin1, Michelle Monje2

  • 1Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorder Center and Harvard Medical School, Boston, MA, USA.

Nature Medicine
|March 8, 2019
PubMed

Insights

Childhood cancers stem from developmental errors, often involving epigenetic changes or fusion oncoproteins rather than high mutation rates. Understanding these origins informs new therapies targeting cancer cells and their environment, and addresses long-term treatment effects.

Area of Science:

  • Pediatric oncology
  • Developmental biology
  • Cancer genomics

Background:

  • Childhood cancers are the primary disease-related cause of death in developed nations.
  • These cancers originate from actively growing tissues, indicating they are fundamentally diseases of dysregulated development.
  • Compared to adult cancers, childhood cancers have a lower mutational burden.

Purpose of the Study:

  • To review the developmental origins of childhood cancers.
  • To examine epigenetic dysregulation in tissue stem/precursor cells during childhood cancer development.
  • To discuss emerging therapeutic strategies and long-term sequelae of childhood cancer therapy.

Main Methods:

  • Review of recent sequencing studies on childhood cancers.
  • Analysis of genomic events, including epigenetic changes and translocations.
  • Synthesis of information on therapeutic targets and treatment side effects.

Main Results:

  • Childhood oncogenesis frequently involves epigenetic alterations or translocations forming fusion oncoproteins.
  • Dysregulated development in tissue stem/precursor cells is a key mechanism.
  • Emerging therapies target both intrinsic cell processes and the tumor microenvironment.

Conclusions:

  • Childhood cancers arise from specific developmental disruptions.
  • Targeting epigenetic dysregulation and fusion oncoproteins offers therapeutic potential.
  • Addressing long-term effects of therapy is crucial for survivors.

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