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Communicating science: Brian Lewis discusses overcoming therapeutic resistance in pancreatic cancer

Pancreatic cancer is the only cancer in which just 10 percent of patients will survive for five years after diagnosis. Brian Lewis, PhD, the George F. Booth Chair in the Basic Sciences and professor of molecular, cell & cancer biology, is hoping to change those grim statistics by studying therapeutic resistance in pancreatic cancer cells.

“Even in those cases where we think the disease is still in the pancreas, it has spread elsewhere in the body,” said Dr. Lewis, associate dean for diversity and pre-matriculation programs in the Morningside Graduate School of Biomedical Sciences and assistant vice provost for outreach and recruitment for UMass Chan Medical School. “Perhaps more importantly, that disease is resistant to the chemotherapies that we currently use, so we need new effective therapies.”

Three decades of research has shown that targeted therapies can be effective. The Lewis lab is trying to identify factors, such as a protein called mTOR, that if removed, can block cancers from forming.

Lewis explained that if his lab took an animal model combining multiple mutations—which causes an aggressive disease—and then blocked mTOR activity, lifespan can be significantly increased. But he said even in those cases where survival is extended, the animals still die from pancreatic cancer.

“This brings us to the idea of combination therapies,” he said.

One example is identifying drugs that can be given at the same time as the other drugs that block mTOR activity so that the ability of pancreatic cancer cells to escape their need for mTOR can be stopped.

Lewis compared this to the treatment of HIV patients. When the drugs that treat the disease were first developed, they targeted one factor. While viral loads initially went down, they would come back up, resulting in the onset or progression of AIDS.

“Now we treat patients with multiple drugs that target multiple parts of the virus at the same time. In doing so, we block the ability of the virus to develop resistance or to escape the effects of the drugs. We want to do something similar for pancreatic cancer,” Lewis said.

He said his lab is interested in understanding three things: if they can identify these combinations; if they can identify markers that predict which pancreatic tumors will be sensitive or will be killed by these drug combinations and which ones will not be; and if they can use the information to begin to understand why some tumors will be killed and why others won’t. That information can be used to tailor therapy to individual patients.

“We’re confident that we can identify those markers and begin to understand how or why these therapies work in the settings that they do,” Lewis said. “This is going to be a very significant undertaking, but we are very excited by the possibility to develop novel therapies for pancreatic cancer, a disease for which this is very much needed.”

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