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Utilising genomic medicine to improve the care of children with cancer

With the advent of genomic technologies, the treatment of cancer is rapidly evolving.

With the advent of genomic technologies, the treatment of cancer is rapidly evolving. Advances in the understanding of the biological drivers of certain cancers have led to the development of targeted therapies, designed to disrupt abnormal disease pathways and lead to the death of cancer cells while sparing healthy cells.

Many of these remarkable advances are applicable in the treatment of children and adolescents with cancer. Still, much about cancer, particularly relapsed and resistant disease, remains unknown. At Children’s Mercy, genomic medicine is considered a critical aspect of the care of every patient treated for cancer.

Offering sequencing to paediatric patients

The Center for Pediatric Genomic Medicine (CPGM) at Children’s Mercy was the first of its kind to be housed within a paediatric hospital. Shortly after its founding in 2011, the CPGM gained national attention for detection of pathogenic genomic abnormalities in neonates by rapid whole genome sequencing. Since then, the CPGM has become a centre for innovation in translational genomic medicine. It offers novel technologies, such as epigenomic, transcriptomic, and single cell sequencing, to patients with malignant and non-malignant diseases.

The centre’s flagship initiative, Genomic Answers for Kids, integrates clinical findings, family history, and biological samples from children and their family members with rare diseases, including cancer. The CPGM is leading the way in advancing genomic medicine for the care of children by collaborating and sharing data with researchers in the medical community.

Clinical testing

The Cancer Genomics Program at Children’s Mercy consists of paediatric providers from the Division of Hematology/Oncology/Bone Marrow Transplantation, the Department of Pathology, and the CPGM. Molecular testing and sequencing are performed in-house, providing the distinct advantage to be able to assess diagnostic clinical data in conjunction with germline (constitutional) and somatic (cancer-specific) variants.

 A team of dedicated cancer bioinformaticists and molecular oncologists analyse the variants and the findings are discussed in a multi-disciplinary tumour board, which includes the clinical paediatric oncologists. Treatments are then tailored to each patient’s needs, resulting in uniquely personalised medicine.

Biobanking and research

Patients and their immediate family members are also given the option to enrol in a biobanking protocol, approved by the Children’s Mercy Institutional Review Board. Patients who opt in agree to donate left-over blood, bone marrow, and tissue samples for long-term storage and research. Each sample is annotated with detailed clinical information regarding the patient’s diagnosis, treatment, and outcome. The Oncology Biorepository is housed within the Children’s Research Institute (CRI) at Children’s Mercy and de-identified samples are available to investigators at Children’s Mercy and in partnering research institutions.

Thanks to the generous support of philanthropic donors and the CRI, the biobank routinely performs sequencing of DNA, RNA, and single cells from each patient’s tumour sample at diagnosis, remission, and if the patient experiences a relapse. Thus, the biobank at Children’s Mercy is generating an enormous resource consisting of invaluable sequencing data, generated prospectively from all types of paediatric cancer samples.

Improving outcomes for infants with ALL

Acute lymphoblastic leukemia (ALL) with KMT2A gene rearrangement is a rare and devastating cancer. Only about one in three infants survives the disease, despite very intensive chemotherapy. Bone marrow transplant and immunotherapies have not improved survival outcomes. At Children’s Mercy, we are working to find targeted cures for this heart-breaking cancer. We have partnered with researchers at Johns Hopkins University School of Medicine to study the genomic biomarkers of infant ALL, by performing genome, exome, transcriptome, methylome, and single cell sequencing of samples from more than 40 infants at the time of initial diagnosis, at remission, and at relapse.

This is the largest study of its kind in infant ALL and the sequencing is being exclusively performed in the CPGM. We hope to uncover new targets for cancer-directed therapies, to improve remission and long-term cure rates for infants with ALL.

Comprehensive care

Children’s Mercy is a full partner and the primary paediatric cancer provider in the National Cancer Institute (NCI)-designated University of Kansas Cancer Center Consortium and is a member of the NCI’s Children’s Oncology Group (COG) Cooperative Group. Children’s Mercy Cancer Center employs 27 paediatric faculty subspecialists with expertise in paediatric cancers, blood disorders, immunotherapies, and stem cell transplantation. The Cancer Center integrates disease-focused programmes, including the leukaemia and lymphoma, brain tumour, and solid tumour programmes, with comprehensive care-focused programmes, such as the Cancer Genomics, Cancer Predisposition (SPoT), Survive & Thrive, Adolescent and Young Adult (AYA), and Spanish-Speaking (HOPE) programmes.

Children’s Mercy Cancer Center offers enrolment in national and international clinical trials, including experimental therapeutics trials, and was one of the first sites in the U.S. to participate in clinical trials of chimeric antigen receptor T-cell therapy (CART) for paediatric acute lymphoblastic leukemia. Every patient treated at the centre receives care from a multi-disciplinary team of paediatric subspecialty providers, with support from nursing, child life, nutrition, pharmacy, psychology, physical and occupational therapy, palliative care team, and social work. 

TAGS: Innovation
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