New potential treatment for aggressive brain cancer in children

April 11, 2017, Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago...Using state-of-the-art gene editing technology, scientists from Ann & Robert H. Lurie Children's Hospital of Chicago have discovered a promising target to treat atypical teratoid/rhabdoid tumor (AT/RT) - a highly aggressive and therapy resistant brain tumor that mostly occurs in infants.

They found that these tumors' growth and tendency to metastasize are regulated by a called Polo-like kinase 4 (PLK4), which is increased in AT/RT. They also have demonstrated that an experimental , a PLK4 inhibitor, stopped growth. Findings were published in Pediatric Blood & Cancer.

"This is the first time that PLK4 has been described as a therapeutic target for brain tumors or in pediatric cancer," said lead author Simone T. Sredni, MD, PhD, Associate Professor of Pediatric Neurosurgery at Northwestern University Feinberg School of Medicine and cancer researcher at the Stanley Manne Children's Research Institute at Lurie Children's.

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 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 cells. "The drug we used to inhibit PLK4 significantly impaired tumor 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 ".

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 pediatric 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 tumors," said Sredni.

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

Explore further: Molecule stops fatal pediatric brain tumor

Related Stories

Molecule stops fatal pediatric brain tumor

February 27, 2017
Northwestern Medicine scientists have found a molecule that stops the growth of an aggressive pediatric brain tumor. The tumor is always fatal and primarily strikes children under 10 years old.

Study maps decade of discovery to potential anticancer agent (w/ Video)

July 17, 2014
The journal Cancer Cell today published research led by Dr. Tak Mak mapping the path of discovery to developing a potential anticancer agent.

Trying to tango with more than two: Extra centrosomes promote tumor formation in mice

January 26, 2017
When a cell is dividing, two identical structures, called centrosomes, move to opposite sides of the cell to help separate its chromosomes into the new cells. More than 100 years ago, scientists observed that cancer cells ...

Molecular 'on switch' could point to treatments for pediatric brain tumor

February 24, 2017
Massachusetts General Hospital (MGH) researchers have identified a mechanism that controls the expression of genes regulating the growth of the most aggressive form of medulloblastoma, the most common pediatric brain tumor. ...

Gene regulatory path revealed as target for therapy of aggressive pediatric brain cancer

February 24, 2015
Working with cells taken from children with a very rare but ferocious form of brain cancer, Johns Hopkins Kimmel Cancer Center scientists have identified a genetic pathway that acts as a master regulator of thousands of other ...

Scientists identify key defect in brain tumor cells

February 1, 2017
In a new study, Yale researchers identified a novel genetic defect that prevents brain tumor cells from repairing damaged DNA. They found that the defect is highly sensitive to an existing FDA-approved drug used to treat ...

Recommended for you

Scientists develop 'world first' melanoma blood test

July 18, 2018
Australian researchers said Wednesday they have developed a blood test for melanoma in its early stages, calling it a "world first" breakthrough that could save many lives.

Early supper associated with lower risk of breast and prostate cancer

July 18, 2018
Having an early supper or leaving an interval of at least two hours before going to bed are both associated with a lower risk of breast and prostate cancer. Specifically, people who take their evening meal before 9 p.m. or ...

Magnetized wire could be used to detect cancer in people, scientists report

July 16, 2018
A magnetic wire used to snag scarce and hard-to-capture tumor cells could prove to be a swift and effective tactic for early cancer detection, according to a study by researchers at the Stanford University School of Medicine.

Researchers suggest new treatment for rare inherited cancers

July 16, 2018
Studying two rare inherited cancer syndromes, Yale Cancer Center (YCC) scientists have found the cancers are driven by a breakdown in how cells repair their DNA. The discovery, published today in Nature Genetics, suggests ...

Researchers map 'family trees' of acute myeloid leukemia

July 16, 2018
For the first time, a team of international researchers has mapped the family trees of cancer cells in acute myeloid leukaemia (AML) to understand how this blood cancer responds to a new drug, enasidenib. The work also explains ...

Scientists sharpen the edges of cancer chemotherapy with CRISPR

July 13, 2018
Tackling unsolved problems is a cornerstone of scientific research, propelled by the power and promise of new technologies. Indeed, one of the shiniest tools in the biomedical toolkit these days is the genome editing system ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.