Integrative Analysis to Identify New Therapies for Pediatric Sarcoma

Although outcomes for children with cancer steadily improve, survival of children with high-risk sarcoma has remained unchanged over the last 20 years. Advances in genomics have led to a much greater understanding about the genetic causes of childhood sarcomas, yet that knowledge has not translated to benefit children in the clinic. A major barrier to progress is that the genetic drivers of childhood sarcoma are not amenable to direct drug targeting. That is because many of the genes that drive pediatric sarcomas are transcription factors, proteins that activate gene expression. Transcription factors lack regions that can be easily used to tailor a specific drug (targeted therapy). There is therefore a pressing unmet need for new methods to identify vulnerable targets in childhood sarcomas. 

Dr. Andrew Kung’s research team has developed a new method to assess the entire signaling network within cancer cells, and to identify the critical signaling nodes, or Master Regulators (MRs), that drive malignancy. The team is using a systems biology approach, where molecular profiling is paired with bioinformatics to identify the key MRs. They have successfully used this method to identify critical MRs in a number of adult cancers. Using this approach, they will analyze single patient samples from children with high-risk sarcomas and identify MRs and then identify drugs that target the activity of the MRs. 

Project Update: Research conducted by Dr. Kung is now supporting a Phase 2 study of the drug Selinexor in the pediatric kidney cancer Wilms tumor and malignant rhabdoid tumor. The trial will began enrolling patients at Memorial Sloan Kettering Cancer Center in 2022, and Dr. Kung and colleagues are in the process of opening the trial at other national sites.