In September’s featured publication, Dr. Nathalie Agar and colleagues show how mass spectrometry imaging can be used to detect pituitary tumors during surgery. This technology may allow surgeons to characterize between the tumor and healthy tissue border in 30 minutes or less, and can be applied for near-real-time detection and surgical decision-making.
In August’s featured publication, Dr. Kieran and his collaborators discuss diffuse intrinsic pontine glioma (DIPG), and the role of epigenetic and genetic mutations within these tumors that will allow the development of novel therapies in the future.
In this month’s featured publication, Dr. Kieran discusses pediatric brain stem gliomas, and how new biological discoveries may lead to potential treatments for these devastating tumors.
In May’s featured publication, Dr. Agar and colleagues developed tools using mass spectrometry to be used to characterize meningioma tumor from healthy brain tissue during surgery. These tools could therefore enable surgeons to detect the borders of the tumor better, and remove only the tumor tissue, leaving the healthy brain tissue behind. These developments could be extended to other brain tumor types in the future, improving surgical procedures.
In our April featured publication, investigators from our Program and their collaborators analyzed the gene expression profiles of 151 pediatric low-grade glioma samples. They discovered significant differences associated with the location of the tumor, the appearance of the tumor and BRAF mutation status. In particular, supratentorial juvenile pilocytic astrocytomas were enriched with genes involved in inflammation. These differences in tumor subtypes further our understanding of the role of location in the brain and the microenvironment of the tumor, and may lead to new targets for therapy in the future.
In this month’s featured publication, Dr. Ligon and colleagues investigate the genetic changes that lead to the transformation of pediatric low-grade glioma to secondary high-grade glioma. Using advanced sequencing techniques, they analyzed 886 patient samples and showed there were recurrent alterations in BRAF (to BRAFV600E) and deletion of CDKN2A, amongst other changes in tumors that progressed to high-grade gliomas. The transformation time from low-grade to high-grade glioma occurs over a prolonged period of time, which provides an opportunity for surgical and targeted therapies to mitigate the outcome of secondary high-grade glioma.
In this month’s featured publication, researchers in Dr. Gray’s group expand upon previous studies of the FGFR receptor, a protein found mutated in a subset of pilocytic astrocytomas. However, a common problem in cancer is development of tumor resistance to chemotherapy over time. Using structure-based drug design, they developed two next-generation covalent inhibitors that can overcome the most common form of resistance, a mutation of the FGFR itself, called the gate-keeeper mutation. These new inhibitors prevented the actions of FGFR on cultured cells, and will serve as prototype inhibitors that will undergo further preclinical validation.
In November’s featured publication, Dr. Kieran discusses diffuses intrinsic pontine glioma (DIPG) biopsy. During the past 50 years, biopsy for these tumors have been discouraged due to excessive toxicity of the procedure. However, Dana-Farber Cancer Institute and Boston Children’s Hospital have recently opened a multi-site national clinical trial of DIPG biopsy and chemotherapy to change the current dogma and improve treatment outcomes for patients.
In October’s Featured Publication, Dr. Sandro Santagata treated a patient with BRAF V600E mutated pleomorphic xanthroastrocytoma (PXA), a rare brain tumor in children and young adults. His team used Vemurafenib monotherapy for the first time in the treatment of V600E-mutated glioma, and saw an encouraging response by the tumor to this approach, leading to the development of a clinical trial for further investigation of BRAF and MEK inhibitors in combination.
In this article in Neuro Oncology, Dr Kieran and others from Dana-Farber Cancer Institute and Harvard Medical School report the results of the RAD001 clinical trial in pediatric patients. They show that treatment with RAD001 was well tolerated in patients with recurrent or progressive low-grade gliomas, and that incorporation of this drug into front line treatment should be considered.