Goals for improving cancer treatment in children

Ushering in the next generation of precision trials for pediatric cancer

Steven G. DuBois, Laura B. Corson, Kimberly Stegmaier, and Katherine A. Janeway

Science (Review article)

Abstract—Cancer treatment decisions are increasingly based on the genomic profile of the patient’s tumor, a strategy called “precision oncology.” Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with cancer. Here, we review key factors influencing pediatric drug development in the era of precision oncology. We describe an emerging regulatory framework that is accelerating the pace of clinical trials in children as well as design challenges that are specific to trials that involve young cancer patients. Last, we discuss new drug development approaches for pediatric cancers whose growth relies on proteins that are difficult to target therapeutically, such as transcription factors.

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Pediatric cancer mutation review

The genomic landscape of pediatric cancers: Implications for diagnosis and treatment

E. Alejandro Sweet-Cordero1 and Jaclyn A. Biegel

Science (Review Artice)

Abstract-The past decade has witnessed a major increase in our understanding of the genetic underpinnings of childhood cancer. Genomic sequencing studies have highlighted key differences between pediatric and adult cancers. Whereas many adult cancers are characterized by a high number of somatic mutations, pediatric cancers typically have few somatic mutations but a higher prevalence of germline alterations in cancer predisposition genes. Also noteworthy is the remarkable heterogeneity in the types of genetic alterations that likely drive the growth of pediatric cancers, including copy number alterations, gene fusions, enhancer hijacking events, and chromoplexy. Because most studies have genetically profiled pediatric cancers only at diagnosis, the mechanisms underlying tumor progression, therapy resistance, and metastasis remain poorly understood. We discuss evidence that points to a need for more integrative approaches aimed at identifying driver events in pediatric cancers at both diagnosis and relapse. We also provide an overview of key aspects of germline predisposition for cancer in this age group.

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Cloud-based access to the fully sequenced genomes of 10,000 pediatric patients with cancer

Genomics Data Could Lead to New Treatments for Children

BY BETH FAND INCOLLINGO

PUBLISHED MARCH 12, 2019

St. Jude Children’s Research Hospital is offering cloud-based access to the fully sequenced genomes of 10,000 pediatric patients with cancer, in the hopes that sharing the information will lead to the highest possible number of treatment breakthroughs.

Called the Pediatric Cancer Genome Project (PCGP), the growing set of data, categorized by cancer type, is meant to help researchers at the Memphis facility and beyond understand the genetic mutations that drive pediatric cancers and find new drugs to treat the diseases.

In whole-genome sequencing, a child’s normal and tumor genes are sequenced and then compared. Mutations that are present in a child’s tumor but not his or her normal genes may be driving the disease, and could be good candidates to target with drugs, said Jinghui Zang, Ph.D., chair of the Department of Computational Biology at St. Jude.

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