Investigators collected the pediatric solid tumor sample , drug-sensitivity data and related information. To improve outcomes for patients with some of the deadliest childhood cancers and scientists made the resource available at no charge to the global scientific community.
St. Jude and the Howard Hughes Medical Institute collaborated to create the resource, known as the pediatric Solid Tumor Network . Michael Dyer corresponding author said, "This research will change that by promoting scientific collaboration to leverage the efforts of patients worldwide."
Children with the muscle tumor rhabdomyosarcoma (pediatric solid tumor) has been identified with the help of this project. Planning has begun to incorporate the finding in an ongoing national clinical trial of the combination therapy high-risk pediatric solid tumor patients.
The tissue samples and other resources needed to advance their understanding and treatment since Pediatric solid tumors are rare. For pediatric solid tumor research, the network has significantly expanded scientific resources.
Researchers developed a system to grow patient's tumors in the same organ in mice and such tumors called orthotopic patient-derived xenografts . The standard approach has been to build patient tumors in the flank of mice.
Dyer said, "The tumor samples were collected at diagnosis, recurrence and autopsy, Many came from patients with recurrent disease, which is important since we had had models of recurrent pediatric solid tumors."
Dyer mentioned, for tracking tumor development and drug sensitivity, tumors should maintain their molecular identity when grown in the same microenvironment in mice and provide more models that are accurate.
Along with whole-genome and whole-exome sequencing and gene-expression profiling , the analysis included the most detailed examination of the genomic or clonal complexity of pediatric solid tumor orthotopic xenografts.
The potential of orthotopic xenografts to speed drug innovation and advance multi-drug chemotherapy, was demonstrated by researchers. To identify the most promising compounds to move to clinical trials, scientists developed a new method that uses orthotopic xenografts to enhance the sensitivity of drug screening. More than 500,000 data points on drug sensitivity, metabolism and related information are included in the results, and these results are available to the global biomedical research community.
Drug sensitivity screening helped identify rhabdomyosarcoma as particularly sensitive to AZD1775, an inhibitor of the enzyme WEE1 that is involved in cell division and expressed at high levels in a variety of solid tumors. Investigators used orthotopic xenografts of high-risk rhabdomyosarcoma to show that the tumors responded when AZD1775 was combined with the chemotherapy drugs irinotecan and vincristine, which are currently used against rhabdomyosarcoma.
Dyer said, "This study shows that orthotopic patient-derived xenografts can serve as a bridge connecting basic and translational research to improve outcomes for patients."