Bringing Precision Cancer Medicine to Children

A UCSF initiative aims to use high-throughput sequencing of pediatric tumors – including whole genome and RNA sequencing – to identify new therapeutic targets for pediatric cancers with high death rates.

UCSF Benioff Children’s Hospitals are poised to launch a Pediatric Cancer Genome Initiative to identify new therapeutic targets for pediatric cancers with high death rates. Despite remarkable successes for many childhood cancers, cancers remain among the leading causes of death for children under the age of 18.

Led by Mignon Loh, MD, and Alejandro Sweet-Cordero, MD – both Benioff chairs of Children’s Health – the initiative builds on the existing UCSF 500 Cancer Gene Panel, which already screens tumors for the most common cancer mutations.

When the program launches this month, any UCSF pediatric cancer patient with a high-risk tumor will have the opportunity to have his or her tumor sequenced at diagnosis or relapse using the UCSF 500 panel, as well as with whole genome and transcriptome (or RNA) sequencing. The latter two tests are not yet approved for direct clinical use, but the information they yield will grow an essential database, enhance understanding of these cancers and facilitate development of future therapies. A comprehensive pediatric-focused hereditary cancer clinic – which could identify mutations that provide information for entire families – will also be an important feature of this initiative.

Genomic Information Could Clarify Therapeutic Options

“Most childhood cancers are curable, but to overcome the next hurdles, we need smarter ways to kill cancer cells,” says Loh, the Deborah and Arthur Ablin Chair of Pediatric Molecular Oncology at UCSF.

Traditionally, finding better therapies for children has been a challenge. Industry concerns about the toxicity of experimental treatments and the complexities of creating liquid formulations make it difficult to open clinical trials for children.

Loh and Sweet-Cordero believe precision pediatric cancer medicine has the potential to change that dynamic. This initiative takes a critical first step by helping to establish large databases of pediatric tumors, as well as new processes that facilitate expert interrogation of those databases. The work will not only identify new therapeutic targets, but will offer immediate clinical applications as well. Recently, Loh’s team used the UCSF 500 panel to discover a novel mutation in a childhood leukemia patient. After review at the molecular tumor board, the patient received an Food and Drug Administration (FDA)-approved small molecule with excellent response.

“The UCSF 500 is already a powerful tool for clinical use and becoming more so, because of expert curation and interpretation by pediatric cancer experts,” says Sweet-Cordero.

RNA Sequencing Enhances Precision

Sweet-Cordero’s group expects to further inform therapeutic options by adding the whole genome and transcriptome sequencing, as well as epigenetic profiling. The additional information could be especially important for pediatric patients, because pediatric cancers tend to have fewer mutational signatures in their DNA. The Sweet-Cordero lab is also developing new tools to identify cancer mutations in the blood of patients with solid tumors, which could reduce the need for invasive biopsies.

“It’s all part of an intensive effort to develop personalized medicine for kids afflicted with cancer, and UCSF is a leader both regionally and nationally,” says Sweet-Cordero.

The UCSF Helen Diller Family Comprehensive Cancer Center has pledged $1.5 million to the effort, with additional funding coming from the UCSF Institute for Computational Health Sciences, led by Atul Butte, MD, PhD. The initiative will also include a partnership with external experts, including David Haussler, PhD, from the UC Santa Cruz Genomics Institute.

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