New potential treatment for aggressive brain cancer in children

Scientists from Ann & Robert H Lurie Children’s Hospital in Chicago found that these tumours’ growth and tendency to metastasize are regulated by a protein kinase called Polo-like kinase 4 (PLK4), which is increased in AT/RT. They also have demonstrated that an experimental drug, a PLK4 inhibitor, stopped tumour growth.

“This is the first time that PLK4 has been described as a therapeutic target for brain tumours or in paediatric cancer,” said Simone T Sredni MD PhD, Associate Professor of Paediatric Neurosurgery at Northwestern University Feinberg School of Medicine and cancer researcher at the Stanley Manne Children’s Research Institute at Lurie Children’s.

Utilising CRISPR/Cas9

Sredni and team were able to identify PLK4 as a potential target for treatment by using a novel gene editing technology called CRISPR/Cas9. It allowed them to mutate individual kinase genes – key regulators of cell function – in order to reveal the kinase that most significantly affected tumour cell growth. Then they targeted that kinase with an available kinase inhibitor, currently being tested for breast cancer.

Sredni and colleagues also found that the PLK4 inhibitor (CFI-400945) was safe for normal tissue, while attacking the cancer cells. “The drug we used to inhibit PLK4 significantly impaired tumour proliferation, survival, invasion and migration, while sparing normal cells,” said Sredni.

Zebrafish larvae

The scientists tested the safety of the drug by exposing zebrafish larvae to extremely high doses of the drug for extended periods of time. They observed that the drug did not affect the fish development, implying that it may be safe to be used in the paediatric population.

The group is currently testing the drug in animal models of AT/RT, as well as other types of brain tumours. Sredni envisions a Phase I clinical trial soon.