A groundbreaking discovery in the fight against childhood cancers has been made by the Children's Cancer Institute. This institute, through its research, has identified a new gene alteration in cancer cells, offering a potential treatment breakthrough. The research, published in the esteemed NPJ Precision Oncology journal, focused on a critical family of genes known as receptor tyrosine kinases, which play a vital role in cell growth and differentiation. Alterations in these genes have long been associated with cancer, and targeting them with TRK inhibitors has shown remarkable success in treating certain cancers.
The Zero Childhood Cancer Program (ZERO), a national precision medicine initiative for children with cancer, was pivotal in this discovery. Led jointly by the Children's Cancer Institute and the Kids Cancer Centre at Sydney Children's Hospital, ZERO conducts comprehensive genomic analyses for every enrolled child. Using ZERO's whole genome sequencing data, researchers identified a novel gene variant in the receptor tyrosine kinase gene NTRK2 in a child with CNS neuroblastoma, a type of brain tumor. This variant, an "internal tandem duplication", is the first of its kind to be identified in this gene, differing from the previously known "gene fusions" associated with NTRK variants.
When the research team modeled this new variant in cancer cells, they discovered an extraordinary sensitivity to TRK inhibition. This finding suggests that existing TRK inhibitor drugs could be highly effective for patients with cancers harboring this novel variant. Dr. Lauren Brown, Senior Research Officer at the Translational Tumor Biology Group and first author of the study, emphasized the importance of understanding genetic variants in driving successful treatments. "When we can identify the specific variants in children's tumor samples and match them with targeted treatments, we can provide more effective treatment recommendations," she explained.
Associate Professor Paul Ekert, who led the research, highlighted their focus on identifying "missed therapeutic opportunities" - instances where existing drugs could be repurposed to benefit a wider range of patients. "Traditionally, treatment has been based on the type of cancer. However, we are adopting a tumor-agnostic approach, matching therapies to specific genetic variants found across various cancers in both children and adults. By identifying a new variant sensitive to an existing therapy, we can potentially expand the reach of that therapy to more patients," he said.
This discovery opens up new avenues for treating childhood cancers and highlights the importance of precision medicine in tailoring treatments to individual genetic profiles. It is a significant step forward in the ongoing battle against childhood cancers, offering hope and potential for improved outcomes.
