New ‘powerful’ drug could treat deadly, drug-resistant forms of children's cancer neuroblastoma

A new treatment may soon be developed for deadly forms of the childhood cancer neuroblastoma with the discovery of a powerful drug that has "unparalleled" strength to fight the disease. Scientists are trying to repurpose the FDA-approved anticancer drug called crizotinib that has been resisted by forms of neuroblastoma.

Neuroblastoma commonly appears as a solid tumour in the chest or abdomen, which contributes to most cancer deaths in children despite many improvements in therapy. However, initial tests of a new drug show a rapid, complete and sustained regression of neuroblastoma tumours in animal models.

Researchers at The Children's Hospital of Philadelphia (CHOP) said the drug would possibly be used in clinical trials in children with neuroblastoma early in 2016. They aim to improve the abilities of crizotinib, which has been approved by the FDA as a treatment for adults with a subtype of lung cancer due to abnormalities in the gene anaplastic lymphoma kinase (ALK).

ALK gene is linked with the risk of developing forms of neuroblastoma. Researchers said abnormal changes in the gene could cause about 14 percent of the high-risk forms of the cancer. Crizotinib works as an ALK inhibitor.

However, in children with neuroblastoma, mutations in the ALK gene have different reactions to crizotinib. The researchers focused on a mutation called F1174L, which has been resistant to the anticancer drug.

To find a new-generation, more effective ALK inhibitor, the researchers examined various next-generation inhibitors and they found the agent called PF-06463922. This agent is being tested in a phase 1/2 clinical trial of an ALK-driven subtype of lung cancer in adults.

The study, published in the journal Cancer Discovery, shows PF-06463922 can inhibit ALK stronger than crizotinib even at far lower concentrations. The agent was found to be more powerful than crizotinib against neuroblastoma tumour cell cultures and in mice with neuroblastoma tumours, which were derived directly from humans.

"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 Dr Yael Mossé, lead researcher and a paediatric oncologist at the CHOP.

"The drug had very broad potency against a range of ALK mutations, so this could become the ALK inhibitor that is prioritised for frontline therapy in patients with ALK-driven neuroblastoma."