Targeted Approach Shows Promise in Treating Deadly Pediatric Brain Cancer

An investigational targeted treatment method was able to shrink tumors caused by medulloblastoma, a form of pediatric brain cancer, according to a recent study published in Nature Communications.
Researchers from Sanford Burnham Prebys Medical Discovery Institute (SBP) developed a targeted treatment that works by blocking a protein called lysine demethylase 1 (LSD1) in group 3 medulloblastoma, the deadliest subtype of the disease.
Medulloblastoma is one of the most prevalent malignant brain tumors in children. More than 350 children are diagnosed with the disease each year. Standard treatment usually involves surgery to remove the tumor, followed by chemotherapy and radiation. There is currently a poor prognosis for those diagnosed with medulloblastoma; one-third of patients will succumb to the disease.
Although chemotherapy and radiation can be effective treatments, they carry a risk of adverse effects due to their high toxicity and can lead to long-term complications, particularly for children. The researchers hope the new therapeutic approach could offer an alternative option for children with the disease to avoid toxicity exposure.  
“Subjecting a developing child to chemotherapy and radiation of the head and spine can leave devastating long-term effects,” said senior author Robert Wechsler-Reya, PhD, professor and director of the Tumor Initiation and Maintenance Program at SBP and program director of the Joseph Clayes III Research Center for Neuro-Oncology and Genomics at the Rady Children’s Institute for Genomic Medicine. “Some children even become intellectually disabled as a result of the treatment, and aren’t able to go to college, live on their own, or achieve other important milestones.”
According to Dr Wechsler-Reya, the findings indicate that a more personalized treatment approach based upon a patient’s specific tumor type might be within reach.
Previously, the researchers’ work had confirmed that a transcription factor called GFI1 is activated in approximately one-third of group 3 tumors.
“In particular, we identify the epigenetic modifier LSD1 as a critical partner to GTFI1, and we demonstrate that these proteins promote oncogenic transformation in part by inhibiting neuronal differentiation,” the researchers wrote in the study. Because transcription factors are difficult to target therapeutically, the researchers found an epigenetic modifier called LSD1, a protein that interacts with GTF11 and can be more easily targeted.
In a mouse model of GFI1-activated group 3 medulloblastoma, the LSD1 inhibitor dramatically decreased the size of the tumors grown under the mouse’s skin. The study showed that treatment with the LSD1 inhibitor shrank the cancer by more than 80%.
According to the researchers, the next step is developing drug delivery technologies that could carry this drug across the blood-brain barrier to the tumor.
“If these approaches are successful, an LSD1 inhibitor could be a promising targeted therapy for children with GFI1-driven group 3 medulloblastoma,” Dr Wechsler-Reya concluded.
Lee C, Rudneva VA, Zapatka M, et al. Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma. Nature Communications. 2019.
Targeted treatment shrinks deadly pediatric brain tumors [news release]. Sanford Burnham Prebys Medical Discovery Institute. Accessed January 24, 2019.

Stay up to date on the latest news in specialty pharmacy by getting Specialty Pharmacy Times in your mailbox or inbox for free!

Click here to sign up for free for the bi-monthly Specialty Pharmacy Times print journal delivered to your address.

Click here to sign up for our email newsletters delivered every Monday, Wednesday, and Friday, in addition to breaking news alerts.

Click here to follow us on Facebook. 

Click here to follow us on Twitter. 

Click here to join our LinkedIn group. 

Related Articles

The supplemental New Drug Application supports the expansion of niraparib’s indication as a late-line therapeutic option for patients with ovarian cancer.
Compared with nontargeted therapy, targeted therapies demonstrated a survival advantage for patients 65 years and older with metastatic renal cell carcinoma.
Patients with multiple sclerosis who switched disease-modifying treatments at least twice had a higher relative risk of developing cancer.
Company Profile >
Industry Guide >
Market News >
Peer Exchange >
Conferences >
Subscribe >
Specialty Times Resources
About Us
Contact Us
Terms & Conditions
MJH Associates >
Pharmacy Times
American Journal of Managed Care
MD Magazine
Targeted Oncology
Physicians' Education Resource
Pharmacy & Healthcare Communications, LLC
2 Clarke Drive
Suite 100
Cranbury, NJ 08512
P: 609-716-7777
F: 609-716-4747

Copyright Specialty Pharmacy Times 2006-2019
Pharmacy & Healthcare Communications, LLC. All Rights Reserved.