New drug treatment for resistance in Children's Cancer

Pediatric oncologists from The Children's Hospital of Philadelphia (CHOP) have reported their latest results in devising new treatments for stubbornly deadly forms of the childhood cancer neuroblastoma. Building on their previous experiences in treating some refractory subtypes of neuroblastoma with the anticancer drug crizotinib, the researchers have identified a powerful new drug with "unparalleled" strength against forms of the cancer that resist crizotinib.
"Our preclinical results provide a strong rationale for fast-tracking this drug into clinical trials in children with neuroblastoma," said study leader Yael P. Mossé, M.D., a pediatric oncologist at The Children's Hospital of Philadelphia. "We expect to begin a clinical trial early this year."
In the current study, PF-06463922 was more powerful than crizotinib in both neuroblastoma tumor cell cultures and in animal models, mice with implanted neuroblastoma tumors derived directly from human patients. Mossé, Lemmon, and colleagues showed that PF-06463922 showed more profound inhibition of ALK than crizotinib, and at far lower concentrations. The tumors in the animals showed rapid, complete and sustained regression.
"The responses we saw in animals were unprecedented in models of ALK-driven neuroblastoma, and bolsters the case for clinical development of this agent for treating children with this subtype of neuroblastoma," said Mossé. "The drug had very broad potency against a range of ALK mutations, so this could become the ALK inhibitor that is prioritized for frontline therapy in patients with ALK-driven neuroblastoma."