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Setting the Course: Genomics Workshop on Childhood Cancers Identifies Research Opportunities

July 17, 2015, by Malcolm Smith, M.D., Ph.D.

Dr. Malcolm Smith

Malcolm A. Smith, M.D., Ph.D.
Associate Branch Chief, Pediatrics
NCI Cancer Therapy Evaluation Program

Our understanding of the genetic changes underlying cancers in children has increased tremendously in the past decade, but there are still critical gaps in our knowledge. Recognizing the importance of closing these knowledge gaps to improve the care of young patients with cancer, NCI recently convened a workshop to discuss the status of genomic characterization for childhood cancers and to identify opportunities for future research.

The meeting, held February 4-5, 2015, brought together several dozen experts, including researchers and clinicians, members of regulatory agencies, and advocates for research on childhood cancers. Over the course of two days, we identified a number of areas for which more research is needed and also identified opportunities to use genomic approaches to gain new insights into childhood cancers.

The workshop concentrated on four major categories of disease: leukemias, embryonal tumors , sarcomas, and brain cancers. Presenters provided summaries of the current understanding of the genomic landscape for specific cancers within each category. We also discussed the translation of genomic discoveries for childhood cancers into new methods of diagnosing and treating the diseases.

One of the main conclusions from the workshop is that we need to further expand our knowledge of the genomics and epigenomics of childhood cancers.

For some of the more common cancers—such as certain leukemias, medulloblastoma, and neuroblastoma—pediatric genomic sequencing projects have analyzed tumors from hundreds of patients (primarily specimens collected at the time of diagnosis). However, for less common childhood cancers, the number of genomically well-characterized specimens is much lower, and we need to more precisely define the prevalence and clinical significance of non-inherited (somatic) genetic alterations for these less common childhood cancers.

We agreed that continued research is needed to identify genomic changes in tumors that have returned after prior treatment. More information about the diversity of genomic changes across multiple tumors within the same individual—and how these changes may affect the response to treatment—is also needed.

Other priorities identified during the workshop include:

  • creating a central repository for data on childhood cancer, which would facilitate collaboration across research teams and help investigators identify less common genomic alterations;
  • developing preclinical models that faithfully replicate the relevant genomic alterations of childhood cancers;
  • identifying treatments that directly or indirectly target genomic alterations that drive childhood cancers and for which there are currently no available targeted agents;
  • identifying inherited genetic alterations that predispose children to cancer and enhancing genetic counseling services at institutions that treat children with cancer.

NCI is supporting research projects that involve the genomic characterization of childhood cancers, and clinical trials are being planned that will help to address some of the research objectives developed at the workshop. For example, the Pediatric MATCH clinical trial is expected to expand our understanding of the genomics of relapsed tumors while also advancing our understanding of the practice of precision medicine.

A detailed summary of the workshop proceedings is now available on the NCI website. I was proud to be part of this important meeting. It has provided a critical framework for our research efforts moving forward and set the stage for more rapid progress against childhood cancers—a goal that we can all agree is of the highest priority.

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