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Precision medicine for paediatric cancer

Research performed over the last several decades has led to an increased understanding of the genetics of cancer.

The clinical application of this knowledge for paediatric cancer has lagged behind studies performed for adults.

In a perspectives article published in the prestigious journal Science, Dr. Jaclyn Biegel, from Children's Hospital Los Angeles, and Dr. Alejandro Sweet-Cordero, of the University of California, San Francisco, survey the landscape of this young field and present opportunities for using genomic information to advance a new era of care for children with cancer.

Cancer arises from genetic changes, including DNA mutations, that are either present at birth, or are acquired over time.

Many adult cancers are initiated by mutations acquired through exposure to substances like smoking and radiation or simply from ageing.

The tumours may contain hundreds of sequence alterations, and identifying which changes drive the growth of the tumours, and impact treatment response can be challenging.

In contrast, paediatric malignancies often develop from a very small number of mutations, only some of which overlap with the types of mutations seen in adult cancers.

Furthermore, an estimated 20% of paediatric cancers arise in children who have a genetic predisposition to malignancy.

For this reason, the clinical genetic assays developed to inform prognosis and treatment decisions for adult cancers have not been as useful in paediatrics.

OncoKids® was one of the first next-generation sequencing panels to detect DNA and RNA changes that characterise paediatric cancers.

The panel was developed at Children's Hospital Los Angeles under the guidance of author Jaclyn Biegel, PhD, FACMG, Director of CHLA's Center for Personalized Medicine.

The OncoKids® panel provides a molecular diagnosis, informs prognosis, and highlights novel therapeutic targets across the broad spectrum of cancers in children, including leukaemias, brain tumours and other solid tumours.

"To truly achieve personalised medicine in paediatric oncology, we need to be able to determine if a child is genetically predisposed to develop cancer," said Dr. Biegel.

In addition to tumour testing, germline testing that uses a sample of a patient's blood, is critical for identifying those children who have a genetic risk for developing cancer in the future.

Besides benefiting the patient, this information has implications for the entire family, since an abnormality that is passed down from parent to child can also raise the risk of developing cancer in siblings.

Although tremendous progress has been made in paediatric cancer care, treatment resistant disease and relapse continue to negatively impact patient outcomes.

Genetic profiling of paediatric cancers is typically done at the time of diagnosis or at the time of relapse to help determine treatment planning.

According to Dr. Biegel, future studies that may be performed over the course of treatment and at remission have the potential to provide critical information about the mechanisms of tumour progression, treatment resistance and metastasis.

Tremendous opportunity exists for changing outcomes in children with cancer by using an integrated approach to evaluating children and their families that includes genomic medicine as a central component in their care.

Source: Children's Hospital Los Angeles



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