Researchers have identified a powerful new drug with "unparalleled" strength against forms of a children's cancer that resist treatment.The researchers focused on devising new treatments for stubbornly deadly forms of neuroblastoma -- a cancer that develops from immature nerve cells found in several areas of the body, including the abdomen, during childhood."Our preclinical results provide a strong rationale for fast-tracking this drug into clinical trials in children with neuroblastoma," said study leader Yael Mosse, paediatric oncologist at The Children's Hospital of Philadelphia in the US."We expect to begin a clinical trial early this year," Mosse noted.
The researchers found that the new drug can treat some forms of neuroblastoma that resist the anti-cancer drug crizotinib.Usually appearing as a solid tumour in the chest or abdomen, neuroblastoma accounts for a disproportionate share of cancer deaths in children, despite many recent improvements in therapy. Neuroblastoma is particularly complex, with a bewildering variety of types and subtypes caused by separate and interacting gene mutations.In children with neuroblastoma, different mutations within the ALK gene respond differently to crizotinib. One particular mutation resisted crizotinib, so the team sought a new-generation, more effective ALK inhibitor.
They tested numerous next-generation ALK inhibitors, and their data allowed them to pursue for further investigation of an agent called PF-06463922.In the current study, the new compound was more powerful than crizotinib in both neuroblastoma tumour cell cultures and in animal models - mice with implanted neuroblastoma tumours derived directly from human patients.The researchers found that that the new compound showed more profound inhibition of ALK than crizotinib, and at far lower concentrations. The tumours in the animals showed rapid, complete and sustained regression when treated with the compound.The study appeared in the journal Cancer Discovery.