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Using Genomics to Better Treat Children with Cancer

, by Daniela S. Gerhard, Ph.D.

Daniela S. Gerhard, Ph.D. is Director of NCI's Office of Cancer Genomics

September is Childhood Cancer Awareness Month.  Every year approximately 13,000 American children and their families receive a cancer diagnosis.  We now know that cancer is not only characterized by the organ that is affected, but by many molecular subtypes that are defined by cancer-driving genetic alterations. 

With a more advanced understanding of these diseases, the scientific and medical communities have made incredible progress in the past 50 years.  For example, 4 in 5 children with Acute Lymphocytic Leukemia (ALL) are now cured, but there are still a number of molecular subtypes that do not respond to treatment.  In addition, the Childhood Cancer Survivor Study is confirming what was feared, that the successful treatment comes at a price for some patients later in life: A number of childhood cancer survivors struggle with heart complications, increased rates of cancer, and other unfortunate effects of successful treatment.   

Precise Treatments for Pediatric Patients

Precision medicine in oncology (precision oncology) aims to address the need for accurate treatment with minimal side effects.  Stratification of patients who are likely to respond, or not, to a treatment regimen is also an important component of precision oncology, be it due to the molecular subtype, tumor heterogeneity, or the genetic background. 

Therapeutically Applicable Research to Generate Effective Treatment (TARGET) was developed to address the need for new treatment modalities and patient classification for pediatric cancers. The initiative, in collaboration with the Children Oncology Group (COG) studied two types of cancer of the blood (with multiple subtypes) and five solid tumors. 

Many scientific papers have been published by the TARGET study teams (see here), including research that identified new subtypes of Wilms tumor (kidney cancer) and Acute Myeloid Leukemia, and more papers are forthcoming. 

TARGETed Clinical Trials

Genomic findings from TARGET have been translated into a number of clinical trials that treat children with cancer based on the molecular characteristics of their tumors.  For example, a clinical trial of ALL run by COG added a treatment arm to include a drug called dasatinib for patients defined as “Philadelphia chromosome-like (Ph-like)”, who are predicted to have a mutation that is specifically targeted by the drug.  Patients enrolled in the trial will undergo molecular testing to determine whether they will receive dasatinib.  

In parallel, the TARGET clinical team has developed another branch of the trial for patients who have Ph-like ALL and another molecular alteration in a pathway that takes growth signals from the environment and converts them into increased cell growth. Children with this molecular profile will receive standard therapy as well as the JAK 2 inhibitor ruxolitinib. These trials aim to prevent tumor recurrence in high-risk patients, potentially curing their disease.

It Takes a Village to Cure a Child

The relative number of pediatric cancer cases is low (in the US, 1.5 million adults are diagnosed with cancer every year); for a given tumor type of childhood cancer there are approximately 300-600 cases per year.  Therefore, international researchers have agreed that collaborations and data sharing will fuel rapid progress in our understanding of pediatric cancers and improve outcomes. 

The National Cancer Institute is spearheading an effort to establish an inventory of biological and clinical studies that used molecular characterization.  While it will not be possible to store all molecular data in one database due to legal concerns, the inventory will include the locations of the databases where the data is available, instructions on how to get approvals, and brief descriptions of the studies.  Researchers and clinicians can then easily merge their results with those obtained by others, increasing their statistical power to detect clinically relevant events present in only 5-10% of patients with a particular disease subtype.  

Through forging a new collaborative model for pediatric cancer research and continuing to interrogate the genomic underpinnings of these diseases, NCI’s Center for Cancer Genomics aims to improve the effectiveness of childhood cancer treatments while preserving the quality of life of young cancer survivors.

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