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Internationally renowned neuro-oncologist Dr. Howard A. Fine of Weill Cornell Medicine and NewYork-Presbyterian will receive a five-year, $6 million National Institutes of Health Director’s Pioneer Award for brain cancer research.

Established in 2004, NIH Director’s Pioneer Awards, part of the NIH Common Fund, will provide nearly $1.2 million annually for five years to a single principal investigator who has demonstrated exceptional creativity and is pursuing a bold new research strategy against a major biomedical challenge. The award will support Dr. Fine’s innovative approach to modeling deadly brain cancers in the laboratory — an approach that could be crucial for the development of effective therapies.

This is the first Pioneer Award received by Weill Cornell Medicine, and will complement an already highly productive brain cancer research program at Weill Cornell’s Sandra and Edward Meyer Cancer Center and the Brain Tumor Center at New York-Presbyterian/Weill Cornell Medical Center and Weill Cornell Medicine.

“We are tremendously excited for Dr. Fine for receiving this wonderful accolade, which reflects his accomplishments as a neuro-oncologist and translational scientist,” said Dr. Augustine M.K. Choi, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine. “Brain cancer is one of the most devastating diseases, and with Dr. Fine’s innovative approach to understanding how these tumors develop and spread, I have no doubt we can make a difference in our patients’ lives.”

“We are delighted that Dr. Fine has been recognized with this prestigious award for his cutting-edge research in brain cancer,” said Dr. Steven J. Corwin, president and CEO of NewYork-Presbyterian. “The innovative and groundbreaking work he is performing in the lab is making real strides towards developing more effective treatments for patients facing this deadly disease.”

“I’m thrilled and honored to have been selected for this award,” said Dr. Fine, founding director of the Brain Tumor Center and chief of the Division of Neuro-Oncology at Weill Cornell Medicine and New York-Presbyterian. “This Pioneer Award will allow us to pursue a brain cancer modeling strategy that represents a bold departure from traditional approaches, which may lead to consequential scientific advances for our patients: new and more effective treatments and therapies. Our work exemplifies the spirit of the NIH’s commitment to high-risk, high-reward research, and I am deeply grateful for this opportunity.”

Scientists for decades have tried to model the most common malignant brain cancers, called gliomas, using patient-derived tumor cell lines cultured in lab dishes or human tumor cells implanted into the brains of mice. Both approaches have significant limitations.

“Traditional lab dish and animal models of gliomas just haven’t been sufficiently representative of clinical disease, and that’s been a big reason for the lack of success therapeutically,” said Dr. Fine, who is also the Louis and Gertrude Feil Professor of Medicine at Weill Cornell Medicine and associate director for translational research at the institution’s Meyer Cancer Center.

Dr. Fine and his colleagues have instead been using advanced stem cell techniques to grow large clusters of functional and interconnected human brain cells, called cerebral organoids, in the laboratory. These cerebral organoids mimic many aspects of a normal 20-week old human fetal brain. Dr. Fine’s laboratory has developed technologies to use these cerebral organoids to examine how individual patients’ gliomas grow and respond to therapies within a realistic biological environment.

“We’ve found, for example, that if we co-culture glioma stem cells from patients with these organoid mini-brains, the glioma stem cells burrow into the mini-brains and begin to grow in a pattern that looks 100 percent like what happens in the patient’s own brain,” said Dr. Fine, who is also a neuro-oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.

Cerebral organoids, with their brain-like environments, have enabled Dr. Fine and colleagues to model brain cancers more accurately on the molecular level. They also have revealed some of the strange, emergent properties of brain cancers that aren’t visible in traditional models. “We can observe the physical networks of microtube structures that connect the individual tumor cells of some gliomas—networks that appear to have a profound impact on these tumors’ ability to resist chemotherapy and radiation,” Dr. Fine said.

With support from the new NIH award, Dr. Fine and his colleagues plan to enhance the realism of their organoid models by adding two vital components: blood vessels with key properties of cerebral vessels, and immune cells that normally reside in or can enter the brain.

Recent research from Dr. Fine and others has found that glioblastoma tumors—the most malignant gliomas—typically harbor genetic mutations that differ from patient to patient and offer no obvious common target for therapies. Part of Dr. Fine’s organoid-based research will therefore involve the development of personalized brain-cancer models using cerebral organoids derived from the cells of patients, which may lead to the development of precision medicine treatment strategies. “We’ll be able to make hundreds of brain organoids for any given patient and use them to screen for drugs that can shrink that patient’s tumor,” he said.

The NIH Director’s Pioneer Award is supported by the National Institutes of Health under Award Number 1DP1CA228040. The content of this press release is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.