For more than three decades, internationally renowned neurosurgeon Dr. Chandra Sen, the Bergman Family Professor of Skull Base Surgery at NYU Langone Health, has provided expert surgical care to patients with chordoma and other skull base tumors. Now, Dr. Sen – a longtime member of the Chordoma Foundation’s Medical Advisory Board – has assembled a team of researchers at NYU Langone to join him in a new initiative to advance chordoma science.
Over the next four years, Dr. Sen and his investigative team will work to discover new therapeutic targets for chordoma, with the aim of improving treatment options for patients. Another project goal is to identify molecular subtypes of chordoma in order to inform more personalized approaches to clinical care. To achieve this, the teams will weave together two approaches:
- Determining the effects of low oxygen conditions (hypoxia) on chordoma biology and immune interactions. Chordomas, unlike many other tumor types, develop few blood vessels; therefore, they tend to have very low oxygen levels relative to normal tissue and even to other tumors. This hypoxia is hypothesized to contribute to chordoma’s ability to avoid being attacked by the immune system and may also represent a vulnerability that could point to new therapeutic approaches. To explore this, the researchers will study chordoma cells grown in the lab under hypoxic conditions and in the presence of immune cells typically found inside tumors. These experiments will help them determine therapeutic approaches that may be effective in overcoming the effects of a low-oxygen environment on the immune response to chordoma. This portion of the project will be led by Dr. David Zagzag, Chief of the Division of Neuropathology at NYU Langone, who has extensively studied the interplay between hypoxia and immune response in brain tumors.
- Conducting comprehensive genomic and immune analyses of chordoma tumor samples. In an approach known as multi-omics, the researchers will combine layers of data – such as genetic, epigenetic, and DNA structural changes in tumor cells and tumor-associated immune cells – to create a big-picture understanding of how these alterations contribute to tumor growth and resistance to therapies. Using tumor samples and clinical data from Dr. Sen’s chordoma patients and other sources, this multi-omics analysis will enable the investigators to identify molecular subtypes of chordoma, which could help predict clinical outcomes, identify patients with high-risk disease, and guide individualized treatment decisions. The approaches employed will complement and be coordinated with other recently initiated multi-omics projects supported by the Chordoma Foundation. This work stream will be led by Dr. Matija Snuderl, Director of Molecular Pathology at NYU Langone and an expert in applying genomics and molecular diagnostics to guide cancer care.
The output of each of these lines of research has the potential to inform the other. For example, epigenetic alterations identified by Dr. Snuderl’s team will be further evaluated by Dr. Zagzag’s laboratory to examine how the changes relate to chordoma’s ability to thrive in hypoxic conditions.
The Chordoma Foundation is partnering with the NYU Langone team in several ways. A key role of the Foundation is to keep the teams connected to critical developments across the global chordoma research field, enabling them to rapidly build on progress in other labs. Where synergies are possible, the Foundation is poised to forge collaborations between NYU Langone and other teams in its network. The Foundation is also providing technical and material assistance to the researchers, including access to chordoma cell lines, mouse models, and associated data. And its close interaction with the NYU Langone team will provide a head start on testing any new therapeutic concepts through the Foundation’s Drug Screening Program as soon as data begin to emerge from this work.
This initiative is powered by the generosity of several donors, chiefly the Bergman Family Foundation, which has made a substantial philanthropic commitment to NYU Langone as well as to the Chordoma Foundation to get this research program started. Through their philanthropic and professional work, the entire Bergman family has long been committed to advancing healthcare: Stanley as Chairman and CEO of Henry Schein Inc., the world’s largest provider of health care products and services to office-based dental and medical practitioners; Dr. Marion Bergman as a retired pulmonologist; together with their children and spouses, Paul and Sara and Edward (Eddie) and Sharon, through supporting various initiatives for equitable access to healthcare globally. Their passion for this particular project is personal, as Eddie is a skull base chordoma survivor who was successfully treated by Dr. Sen and his partners at NYU Langone. Through this experience, they saw an opportunity to help marry the institution’s excellence in chordoma care with its strong research capabilities, bringing NYU Langone to the forefront of chordoma science, and drawing much needed attention to chordoma. The Foundation is thrilled that the chordoma community will benefit from their generosity and looks forward to working with the NYU Langone team to further understanding of the disease.