More effective treatment could be on the horizon for children diagnosed with high-risk neuroblastoma, a childhood cancer with a 5-year survival rate of only about 50%, thanks to new research published online by Nature Communications.
An international collaboration between Children’s Cancer Institute, Children’s Hospital of Philadelphia (USA), and precision oncology company Repare Therapeutics (Canada), the research found that a new therapy, known as RP-1664, has potent activity against high-risk neuroblastoma in clinically relevant models of the disease.
‘This research was very much a combined effort, bringing together expertise in drug development and tumour biology with proof-of-principle testing using internationally renowned mouse models of high-risk neuroblastoma,’ said Professor Michelle Haber AM, head of the Experimental Therapeutics and Molecular Oncology Group at Children’s Cancer Institute, and a senior author on the paper. ‘Evidence of activity for new drugs in combination with existing therapy, guided by an understanding of biology and using the most realistic models, is crucial to advancing new treatments for this devastating disease.’
The research follows recent findings that cancers with a particular molecular alteration (17q/TRIM 37 gain) are vulnerable to therapies known as polo-like kinase 4 (PLK4) inhibitors, of which RP-1664 is one. In the current study, researchers showed that this molecular alteration was a defining feature of high-risk neuroblastomas, rendering them hypersensitive to RP-1664 and presenting a “tremendous opportunity” for biomarker directed clinical development of this novel agent.
In preclinical testing, RP-1664 showed striking activity when used as a monotherapy in models developed from diverse neuroblastoma patients with 17q/TRIM 37 gain. In a model that allows realistic modelling of the immune system, combining RP-1664 with established chemotherapy and anti-GD2 antibody immunotherapy was particularly effective, leading to long term tumour-free survival.
‘RP-1664 showed remarkable efficacy when combined with standard-of-care chemoimmunotherapy in our experiments,’ said Professor Haber. ‘These results are very exciting, since they suggest that the same combination in children could also be effective.’
‘This new therapy shows excellent potential for clinical development as a treatment for children with relapsed or refractory neuroblastoma, as it builds directly on established treatments. We will be watching next steps with great interest.’
Read the full research paper online
