Taking Aim at Molecular Targets for Meningiomas & Pituitary Tumors

black and white image of DNA double helix
Image courtesy of Wenya Linda Bi, MD, PhD

Meningiomas and pituitary tumors traditionally have been regarded as surgically treated disease. However, some patients with these tumors face recurrence, premature morbidity and mortality. This challenge has motivated researchers at Brigham and Women’s Hospital to zero in on molecular targets that shed light on prognosis and suggest novel pathways for biological treatments.

Advances in surgical technique, including many pioneered by members of the Department of Neurosurgery at Brigham and Women’s Hospital, such as Ossama Al-Mefty, MD, and Edward R. Laws, MD, have made it possible to operate more successfully than ever on a wide range of tumors. But surgery and radiation may not be able to vanquish high-grade recurrent meningiomas, pituitary adenomas, craniopharyngiomas, chordomas and other tumors in challenging anatomical locations.

“For a subset of patients with aggressive subtypes of skull base tumors, the underlying biology of the tumors sometimes defeats existing treatments, which motivates us to improve our understanding of these tumors,” said Wenya Linda Bi, MD, PhD, Assistant Professor of Neurosurgery and a core member of the Brigham’s Center for Skull Base and Pituitary Surgery. “We are working to develop a molecular taxonomy and better predictive tools for skull base tumors, especially meningiomas and pituitary tumors, with the understanding that existing histopathology classification schemes have limitations in predicting outcomes and response to treatment. Furthermore, decoding the genomic and immunologic landscape of these tumors may allow development of novel pharmacotherapeutic strategies.”

For meningioma, Bi and colleagues are beginning to unveil the complexities of the genomic and immune microenvironment, which may have direct implications for devising immune modulation strategies that are best suited for these tumors.

A study of Genomic Landscape of High-Grade Meningiomas by Bi and others analyzed the genomes of 134 grade II-III meningiomas (and compared them with data from nearly 600 other meningiomas) to shed light on their mutation burden, chromosomal signature, and complex rearrangements. The work identified immense intratumoral heterogeneitywithin meningiomas, which may suggest resistance to targeted therapies. The research also produced a proof-of-concept that a cancer immunogenomics approach to high-grade meningiomas may be promising.

Learn more about Dr. Bi’s research in molecular classification of skull base tumors and treatment implications of these advances.

Co-authors of this paper were affiliated with Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard where foundational work in the field has been done. “That is a strength here in the Boston community,” Dr. Bi said. “There are few places with such concentration of technological resources and passion for decoding the biology of skull base tumors.”

In a study of pituitary tumors, a similar collaboration  with Dana-Farber and the Broad Institute defined molecular subtypes of pituitary adenomas operated on at Brigham and Women’s Hospital using next-generation sequencing. They expanded this study in a clinical cohort of 127 patients with pituitary tumors, who underwent routine molecular profiling, and observed canonical mutations in hormone-secreting pituitary adenomas and craniopharyngiomas.

Dr. Bi with collaborators Ian Dunn, MD, and Edward R. Laws, MD, are further interrogating the immune profile of pituitary tumors and its association with their genomic signature.

The growing genetic subsets identified for meningiomas and pituitary tumors suggests the promise of useful biomarkers and pharmacologic targets.Building on the progress made in classifying tumor biology in just a few years, translational questions are now being addressed. Prospective trials that currently are recruiting patients will test a number of medical therapies for meningioma, and some are integrating genomic inclusion criteria, Dr. Bi noted.

“Despite knowing that we have excellent surgical strategies, we realize the aggressive biology and nature of some of these tumors continues be a challenge,” said Dr. Bi. “That is what inspired us, in a short period of time, to make so many advances on tumor biology, both genomic and immune. We are in the midst of understanding these complex tumors. It’s not as clear cut or straightforward as just finding the targets and blocking them, but we are committed to continuing our investigations until we can provide a better solution for these patients.”

Hear more about the Skull Base and Pituitary Surgery Program at Brigham and Women’s Hospital.

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