Soon, a treatment for aggressive brain cancer in kids
Washington D.C. [USA], Apr 12 : A team of researchers has discovered a promising target to treat atypical teratoid/rhabdoid tumour (AT/RT), a highly aggressive and therapy resistant brain tumour that mostly occurs in infants.
Using state-of-the-art gene editing technology, the scientists from Ann & Robert H. Lurie Children's Hospital of 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 lead author Simone T. Sredni.
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 tumor 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. "This may be a paradigm shift for the treatment of AT/RT and possibly other paediatric brain tumours".
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.
"This could also be an opportunity for a precision medicine approach as we can stratify patients who are eligible for treatment with the drug by investigating the level of PLK4 expressed in their tumours," said Sredni.
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.
The findings are published in the journal Paediatric Blood & Cancer. (ANI)
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