Roel Verhaak, PhD, Harvey and Kate Cushing Professor of Neurosurgery, was at a recent brain cancer workshop at Cold Spring Harbor Laboratories with other luminaries in the field when something stark struck them.

“We had a similar workshop before the pandemic, and we realized that we had made very little progress in those five or six years, which is a bit disheartening because there is no doubt we have the best scientists working to understand this disease,” Verhaak says.

As the world commemorates Brain Cancer Awareness Month in May, Verhaak says the research community has a message to share.

“We’re recognizing that we need a paradigm shift – that we need to approach the disease differently than we have so far – and that we need different strategies to try to attack the complexities of the disease.”

Verhaak is among those at the forefront of research being done at Yale Cancer Center to improve outcomes for patients with gliomas, tumors that develop from glial cells in the brain and spinal cord. As a member of the Department of Neurosurgery, he works with talented brain surgeons, including Jennifer Moliterno, MD, FAANS, professor of neurosurgery and chief of neurosurgical oncology.

“Dr. Moliterno definitely deserves all the credit because it’s an extra step on her part and her team’s part to preserve tissue for us, and she does a great job at that,” he says. “She is one of the best in her field and she is also a brilliant collaborator.”

Phase Zero Trials

One of the strategies Verhaak supports is investing more in Phase Zero trials, where the patient gets cancer therapy two weeks before the primary treatment of surgery. Phase Zero trials use small doses of a new drug in a few people. Among the things researchers try to determine are whether the drug reaches the tumor, how the drug acts, and how cancer cells respond to it. Phase Zero trials are done prior to initiating a more traditional Phase One testing.

“This gives us the chance to take some of the tissue obtained during surgery and measure whether that treatment brings about any changes to the tumor. This information is particularly valuable in the setting of experimental therapies where we are trying to understand if this new approach is effective,” he said.

Verhaak and other Yale researchers use the tissue provided by Moliterno and other neurosurgeons to map a response to the treatment.

“We do deep molecular analyses on these tissue samples – we basically general millions or billions of data points. By getting tissue from a patient who is newly diagnosed, then getting tissue from that same patient after they have received treatment, we can compare the profile of the newly diagnosed tumor to the one that has been treated, and try to understand how the treatment changes the tumor, and how that change drives the tumor to become more resistant to further treatments. We also try to identify mechanisms the tumor uses to become treatment resistant, and we can target those mechanisms to make the tumors essentially sensitive to treatment again.”

Patient Advocate Perspective

Verhaak also works with patient advocates in the Connecticut brain tumor community. “We recognize that patients should have a say in how we design our studies,” he says. This is a common practice at Yale Cancer Center, where researchers value input from patient advocates and work closely with them to direct cancer research.

Caitlin Celella became a patient advocate for a grant application for brain cancer research after Moliterno approached her about serving in the role.

“Dr. Moliterno performed three successful craniotomies on my husband, Andy, who was diagnosed with brain cancer in 2019 at the age of 30,” Celella says. “Dr. Moliterno, her team, and everyone at Smilow gave me and my young sons (Ralphie and Vinny) an extra four years with Andy. He passed away in June of 2023.”

In her role as patient advocate for the grant proposal, Celella and another advocate provide the patient’s perspective to the grant application team, comprised of researchers, physicians, and surgeons. Their input is particularly important to the team as it decides which research studies to include in the proposal. While researchers and doctors focus on clinical and laboratory work, the patient advocates raise issues such as what the study may mean for a patient's daily life, how more often they would have to visit YNHH, and how the study might restrict their activities.

“Although we never went to medical school, Dr. Verhaak and his team made sure to ask for our input,” Celella says. “I feel like a valued member of the team.”