Understanding brain tumors is key to advancing promising research

Vinay Puduvalli

The inner workings of the brain are a mystery.

But now, with the aid of genetic sequencing, neuro-oncologists have begun to unravel some of the inner workings of brain tumors and are developing new, more promising treatments.

“After years of frustration, it’s incredibly encouraging to see the advances we are making,” said Vinay Puduvalli, MD, director of the Division of Neuro-Oncology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James). “We have this sudden and deep insight into brain tumors that has allowed us to see that what we thought was one type of tumor is many types with the same appearance, yet many different behaviors.”

Puduvalli and his colleagues at the OSUCCC – James are immersed in research and clinical trials that utilize biological therapies to wake up the body’s immune system and attack cancer cells in brain tumors, and are also targeting the signaling hubs in cancer cells that advance their rapid growth.

“Brain tumors are very complex,” he explained. “It’s like fighting many types of enemies within a tumor, and when you beat one, another rises. Are there similarities among tumors or is each one unique? We are getting closer and closer to that understanding, and that is why this is such an incredibly rewarding time to be in this field.”

May is Brain Cancer Awareness Month, and a good time to check in with Puduvalli to better understand the work he and the team at the OSUCCC – James is doing.

There will be about 24,000 new cases of brain cancer diagnosed in 2016, according to the National Cancer Institute, and about 16,000 deaths.

“Brain tumors are extremely rare,” Puduvalli said. “But they are one of the deadliest forms of cancer.”

There are two types of brain tumors: Primary tumors that develop in the brain; and secondary tumors that start elsewhere in the body, metastasize and travel to the brain.

Secondary brain tumors occur more frequently and are more complicated to treat. In secondary tumors “there are issues going on in the brain and in other areas of the body of the patient,” Puduvalli said. “You have to maintain a balance in treating both, and this is where the OSUCCC - James really shines. We have all the specialties and experts here, the vision that needs to be in place and the collaboration that is necessary.”

Viral immunotherapy is an exciting new area of research.

“The idea is to inject a virus into the brain tumor,” Puduvalli said, adding he and his team are working with Adenovirus, a common cold virus. The virus exposes the abnormal proteins in the cancer cells that the cancer cells have deviously been hiding from the body’s immune system. “And then we add another drug that goes through the body and wakes up the immune system – a check point inhibitor.”

This two-pronged attack has shown great promise in laboratory tests. The next step is approval for clinical trials.

“We are in the midst of obtaining regulatory approval and then we can offer it to patients,” Puduvalli said.

Another important area to understand is how cancer cells communicate with one another.

“They have signal hubs that send out signals for growth, and they communicate at a much faster rate than normal cells,” said Puduvalli, who uses an assembly line analogy to explain this complicated process.

Think of two identical factories. The first produces 100 products a day, while the second produces 1,000 of the same product daily.

“To do this, you have to speed up the assembly line, and the cancer cells need to function at a much higher level of efficiency,” Puduvalli said. “This puts pressure on the cancer cells to divide faster and the ones that can do this grow and survive very efficiently.”

Heat shock proteins within the cancer cells enable it to survive and thrive under these stressful “assembly line” conditions – and also present a target to attack.

“Every protein has a certain configuration that is necessary for it to be functional,” Puduvalli said. “If it is not folding correctly, it can not function. And if we disable the folding process, they can’t function.”

Puduvalli's lab is testing a new drug – HSP90 – that seems to inhibit the heat shock proteins in brain tumors and disable their signaling hubs.

“It is an investigational drug that is not yet FDA-approved and has been tried in other forms of cancer, but not brain tumors,” Puduvalli said. This research is unique to Puduvalli and his lab, and he has applied for National Cancer Institute approval for a clinical trial.

What drives Puduvalli is simple: His patients.

“All you have to do is walk through the clinic and see these people whose lives have been so deeply affected,” he said. “Brain tumors completely shatter the lives of patients and their families … And the optimism from all this new research and the fact that we are making advances is the reason we can get up and go back to work and fight again.”