PHOENIX, Ariz. – October 5, 2021 – While the survival rates of children with cancer are improving, not all children respond to current medical treatments. Cancers in children, adolescents and young adults may be resistant to medical treatments or may recur even if initial treatments appear successful.
Findings from a 10-year study led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, and in collaboration with the Beat Childhood Cancer Research Consortium, suggest that deeper genomic analysis and therapies that rely on the immune system of the body may provide greater benefit to the patient.
The study, published today in Cancer Research, a journal of the American Association for Cancer Research, used genomic sequencing to analyze 250 solid tumors from 202 young patients enrolled in the Beat Childhood Cancer Research Consortium’s clinical trials in more than 40 US hospitals and universities . Cancer is the leading cause of disease-related death in children in the country.
The study focused on those children and young adults whose cancers were refractory, meaning they were resistant to treatment, or had relapsed, meaning the cancer returned after a period of initial improvement. Researchers found that refractory or recurrent tumors had a higher number of genetic mutations than tumors at diagnosis. More than two in five tumors mutated as a result of chemotherapy.
“Sometimes, despite the best medical care and significant advances made in cancer treatment in recent years, tumors come back,” said Sara Byron, Ph.D., an associate professor in TGen’s Integrated Cancer Genomics Division, and a researcher. from the leading authors. “Relapses probably occur because initial treatments fail to eliminate some of the original cancer cells. We need to know why this is happening and find ways to treat these tumors more effectively.”
Will Hendricks, Ph.D., an assistant professor in TGen’s Integrated Cancer Genomics Division, and another of the study’s lead authors, said this study — with its high demand for computing speed and computing power — was only possible because of a multi- institutional effort and the critical support of Dell Technologies.
“This groundbreaking study provides unique insights gained from in-depth genomic analysis of some of the most clinically challenging tumor types in children,” said Dr. hendricks.
By partnering with Dell Technologies, TGen has reduced the computation time for these tumor analyzes from weeks to hours. This was instrumental in providing timely results for the patients and their oncologists. The power of applying the latest technologies to help decipher the complexity of the human genome continues to drive better treatments for patients.
Of the 202 patients whose cancers were sequenced, 20 patients had multiple recurrences of their cancers, allowing their tumor genomes to be sequenced at each recurrence. This helped uncover the evolution of genetic changes in their cancer over time and revealed new targeted therapies in several cases.
Jeffrey Trent, Ph.D., TGen president and research director, and one of the study’s senior authors, noted that many of the childhood cancers showed different mechanisms of immune evasion and generally did not show infiltration by immune cells, although these finding may open the door for additional research that could identify and develop new therapeutic options.
“Between the potential for targeted therapies and new ways to use the immune system against cancer, we are encouraged by the potential to use the information from our research to help these children, give them and their families answers and hope for the future.” said Dr. Trent, who also heads TGen’s Genetic Basis of Human Disease Division.
The study’s other senior author, Giselle Saulnier Sholler, MD, agreed, adding that most patients in this study had tumors expressing multiple neoantigens, which are proteins on the surface of tumor cells that serve as therapeutic targets. can be used. More than half of the patients in the study expressed five or more neo-antigens.
“This research highlights the importance of genomic sequencing for pediatric cancers at any progression as we gain insight into how tumors mutate over time and mechanisms of resistance, which could have important clinical implications,” said Dr. Sholler, director of the Isabella Santos Foundation Solid and Rare Tumor Program at Atrium Health Levine Children’s, where she is a professor of pediatric oncology. dr. Sholler is president of the Beat Childhood Cancer Research Consortium.
Javed Khan, MD, deputy chief of division of the Division of Genetics and chief of the Division of Oncogenomics of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, noted that the study was so complex that 46 diagnostic types of highly aggressive childhood cancers, and is the result of extensive multi-year collaborations between academia, industry and government.
“This study represents an important multi-omic analysis of tumors from 202 children and young adults with difficult-to-treat cancers,” said Dr. Khan, an ImmunoGenomics expert and one of the authors of the study. “The data – available at clinomics.ccr.cancer.gov/clinomys/public/login for in-depth research by clinicians and scientists – are a valuable contribution to pediatric oncology.”
Also contributed to this study were: Dell Children’s Medical Center, Penn State College of Medicine, St. Joseph’s Children’s Hospital, Helen DeVos Children’s Hospital, Rady Children’s Hospital, Connecticut Children’s Medical Center, Kapiolani Medical Center for Women and Children, Children’s Hospitals and Clinics of Minnesota, Arkansas Children’s Hospital, University of California San Diego, Medical University of South Carolina, Saint Louis University School of Medicine, Frederick National Laboratory for Cancer Research, and Ashion Analytics.
Major funding for this study — Genomic and transcriptomic analysis of recurrent and refractory solid tumors in childhood reveals a diverse molecular landscape and mechanisms of immune evasion — was provided by Dell Technologies in support of its commitment to use its technology and scale to advance health, education and economic opportunity initiatives. Additional funding was provided by the TGen Foundation, Beat NB Foundation, Meryl and Charles Witmer Foundation, Four Diamonds, Hyundai Hope on Wheels, Hartwell Foundation, Padres Pedal the Cause, and Reid R. Sacco Adolescent and Young Adult Cancer Alliance.
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