Research Summary

Pediatric brain tumors are the second most common form of cancer and the leading cause of cancer-related morbidity and mortality in pediatrics. Until recently, the majority of research in pediatric brain tumors was focused on the highly aggressive embryonal tumors, such as medulloblastoma, and there have been recent dramatic advances in the understanding of this subset of tumors.

However, more than half of childhood primary central nervous system tumors are gliomas and, unlike the situation in adulthood, low-grade gliomas constitute most pediatric gliomas. Pediatric low-grade gliomas arise throughout the nervous system and, despite their often indolent nature — dependent on their location in the nervous system — they may not be amenable to safe, extensive resections and can result in significant morbidity and, at times, mortality.

Radiation has been a conventional second step in therapy when surgery is not deemed feasible. In many children, this can result in excellent long-term control, but it also may result in long-term sequelae. These sequelae include acute deterioration due to radiation-induced necrosis and swelling, but radiation-associated intellectual deteriorations over time, hormonal deficiencies, cerebral vascular injury and secondary brain tumors are more frequent.

Because of these complications, alternative means have been sought to treat aggressive, nonsurgically resectable low-grade gliomas. During the past 2 decades, chemotherapy has been found to be surprisingly effective, despite the apparent slow growth pattern of these tumors. Chemotherapy was initially used to primarily delay the need for radiation therapy and, in up to one-third of patients, it may obviate the need for radiotherapy.

Despite the benefits of chemotherapy, such treatments are often only of transient benefit, and there have been recent concerns raised that despite radiographic stability during and after treatment, patients will continue to lose neurologic function, especially those patients with tumors in the visual pathway who may lose vision over time despite apparent successful treatment. For these reasons, alternative treatment options are being sought.

Currently, there is tremendous interest in utilizing other biologic approaches for pediatric low-grade gliomas. Probably more than three-fourths of pediatric low-grade gliomas are pilocytic astrocytomas. The vast majority, if not all, of pilocytic astrocytomas have been shown to have abnormalities in the RAS-MAPK signaling pathway. Abnormalities in BRAF (a component of the pathway), either activating fusion protein abnormalities or point mutations, have been shown to be present in most cases, and these abnormalities are molecular targets.
Studies are underway to evaluate drugs that inhibit the effects of BRAF-point mutations and other studies attempting to block RAS-MAPK kinase signaling with the use of MEK inhibitors (MEK being a component of the signaling pathway one step after BRAF). Other studies are attempting to turn off aberrant cellular signaling of pediatric low-grade gliomas further downstream by interfering with mTOR.

These exciting new approaches will need to be carefully evaluated, not only regarding efficacy in tumor control but also their ability to improve neurologic and/or visual function without causing short- and long-term unacceptable sequelae.

However…there is reason to be tremendously optimistic about the future of treatment for pediatric low-grade gliomas and the ability of molecularly targeted therapies to change the way patients with recurrent disease — and, in time, those with newly diagnosed disease — will be treated in the near future. (Dr. Roger J Packer, MD, Children’s National Medical Center, Center for Neuroscience Research, Director, Brain Tumor Institute.

Over the course of the past 11 years, A Kids’ Brain Tumor Cure has raised over $16.5 million and has funded a dozen international conferences, 5 clinical trials and 4 dozen research projects.


Research Projects

AKBTC Sponsored Research:

Clinical Trials

We hope you will return to this section frequently to explore the new studies that are being funded by A Kids’ Brain Tumor Cure Foundation (aka PLGA Foundation). Grant applications are accepted and grants are approved all year long.

With continued education and research funds, we can begin to imagine targeted therapies that arrest the development and potentially cure patients suffering from the most common forms of children’s brain tumors.

Please Donate to A Kids’ Brain Tumor Cure Foundation (aka PLGA Foundation) today. Your generosity can bring us one giant step closer to a 100% cure!