Nav: Home

New drug combination shows promise for common pediatric brain tumor

March 21, 2019

A new combination treatment aimed at resistant and recurrent low-grade gliomas slowed tumor growth and killed tumor cells in laboratory and mouse models.

Researchers at the Johns Hopkins Kimmel Cancer Center and the Johns Hopkins University School of Medicine combined carboplatin, a standard chemotherapy drug that works well against these brain tumors, and everolimus, which blocks an enzyme called mTOR that was shown in earlier research to fuel the growth of these tumors. The combination increased DNA damage and cell death in laboratory models. Their findings were published in the Feb. 14, 2019, issue of Neuro-Oncology.

Pediatric low-grade glioma is the most common brain tumor in children and can often be treated with surgery alone. However, some patients have tumors in locations that make surgery too risky, such as near optic nerves or in the mid-brain area, or have their tumors grow back after surgery.

Eric Raabe, M.D., Ph.D., associate professor of oncology and pediatric brain tumor expert at the Johns Hopkins Kimmel Cancer Center, says tumors recur in about 50 percent of patients treated for low-grade glioma and require additional treatment with chemotherapy. Recurring tumors are often resistant to chemotherapy. The researchers wondered whether combining carboplatin and everolimus would be more effective.

When treated with carboplatin alone, four different human cell lines of low grade glioma cancer cells did not respond to the drug or kept growing. Similarly, some cell lines were resistant to everolimus alone.

When they treated the same cell lines with a combination of carboplatin and everolimus, the cells died or grew slower, and the researchers saw similar results in mouse models with no added toxicity.

"We saw dramatic growth inhibition after only a low concentration of everolimus was combined with the carboplatin," says Raabe. "We found that everolimus disrupted a key mechanism the cancer cells use to detoxify carboplatin. The ability of everolimus to increase the power of carboplatin suggests this combination could be used effectively in patients."

In a previous clinical study in 2014, Raabe and other researchers were able to confirm the safety of the mTOR-blocking drug everolimus in patients with pediatric low-grade glioma and found some patients responded to the medicine. However, they never tested tumor tissue from those patients to understand the molecular role of mTOR.

"The current nationwide clinical study of everolimus in pediatric low-grade glioma requires that some tumor tissue from each patient be evaluated for expression of mTOR markers that might predict response to everolimus," Raabe says. "In this way, we hope to figure out who is most likely to respond to the drug, so that we can move closer to our goal of giving the right medicine to the right patient at the right time. In the future, we may be able to give everolimus along with carboplatin to patients with high-level mTOR expression. Based on our research, we predict that these tumors will likely be resistant to carboplatin unless we simultaneously block mTOR."
-end-
In addition to Raabe, other researchers in the study include Brad Poore, Ming Yuan, Antje Arnold, Antoinette Price, Jesse Alt, Jeffrey A. Rubens, Barbara S. Slusher and Charles G. Eberhart.

This work was supported by Johns Hopkins Institute of Clinical and Translational Sciences, the Sidney Kimmel Comprehensive Cancer Center, Giant Food Pediatric Cancer Research Fund, Imagine an Answer to Kids' Brain Cancer foundation, and A Kids' Brain Tumor Cure foundation.

There were no conflicts of interest in connection with this study.

Johns Hopkins Medicine

Related Chemotherapy Articles:

Chemotherapy drug may increase vulnerability to depression
A chemotherapy drug used to treat brain cancer may increase vulnerability to depression by stopping new brain cells from growing, according to a new King's College London study out today in Translational Psychiatry.
Sperm changes documented years after chemotherapy
A Washington State University researcher has documented epigenetic changes in the sperm of men who underwent chemotherapy in their teens.
Depressed patients are less responsive to chemotherapy
A brain-boosting protein plays an important role in how well people respond to chemotherapy, researchers report at the ESMO Asia 2016 Congress in Singapore.
Breast cancer study predicts better response to chemotherapy
It is known from previous research that the ER-beta estrogen receptor often has a protective effect.
Personalizing chemotherapy to treat pediatric leukemia
A team of UCLA bioengineers has demonstrated that its technology may go a long way toward overcoming the challenges of treatment for acute lymphoblastic leukemia, among the most common types of cancer in children, and has the potential to help doctors personalize drug doses.
How gut microbes help chemotherapy drugs
Two bacterial species that inhabit the human gut activate immune cells to boost the effectiveness of a commonly prescribed anticancer drug, researchers report Oct.
Molecule prevents effect of chemotherapy
For the last three years the research team has been working on the development of a so-called biomarker to predict treatment effectiveness.
Study provides new clues to leukemia resurgence after chemotherapy
For the first time, researchers have discovered that some leukemia cells harvest energy resources from normal cells during chemotherapy, helping the cancer cells not only to survive, but actually thrive, after treatment.
Dialing up chemotherapy for pancreatic cancer with ultrasound
Researchers at Haukeland University Hospital in Bergen, Norway have combined a laboratory ultrasound technique called 'sonoporation' with the commercially-available chemotherapy compound Gemcitabine to increase the porosity of pancreatic cells with microbubbles and to help get the drug into cancer cells where it is needed.
Vitamin A may help improve pancreatic cancer chemotherapy
The addition of high doses of a form of vitamin A could help make chemotherapy more successful in treating pancreatic cancer, according to an early study by Queen Mary University of London.

Related Chemotherapy Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Climate Crisis
There's no greater threat to humanity than climate change. What can we do to stop the worst consequences? This hour, TED speakers explore how we can save our planet and whether we can do it in time. Guests include climate activist Greta Thunberg, chemical engineer Jennifer Wilcox, research scientist Sean Davis, food innovator Bruce Friedrich, and psychologist Per Espen Stoknes.
Now Playing: Science for the People

#527 Honey I CRISPR'd the Kids
This week we're coming to you from Awesome Con in Washington, D.C. There, host Bethany Brookshire led a panel of three amazing guests to talk about the promise and perils of CRISPR, and what happens now that CRISPR babies have (maybe?) been born. Featuring science writer Tina Saey, molecular biologist Anne Simon, and bioethicist Alan Regenberg. A Nobel Prize winner argues banning CRISPR babies won’t work Geneticists push for a 5-year global ban on gene-edited babies A CRISPR spin-off causes unintended typos in DNA News of the first gene-edited babies ignited a firestorm The researcher who created CRISPR twins defends...