Dr. Nipun Merchant Leads New Pancreatic Cancer Study

Appointed to the PANCAN Medical Advisory Board

Nipun Merchant, M.D., Vice Chair of Surgical Oncology Services and Chief of the Division of Surgical Oncology at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, has received a $300,000 grant from the Pancreatic Cancer Action Network (PANCAN), a national organization creating hope in a comprehensive way through research, patient support, community outreach and advocacy for a cure for pancreatic cancer. The funds will be used to further research on overcoming resistance to therapy associated with certain gene mutations in pancreatic cancers.

“Pancreatic cancer is one of the most difficult human malignancies to treat because it is resistant to almost every type of treatment,” said Merchant, who is also the Alan S. Livingstone Endowed Professor of Surgery at the Miller School. “This grant will enable us to continue studying effects of the mutations and how to further optimize combination therapy with the goal of getting the treatments into clinical trials.”

Merchant said that a key genetic mutation that occurs in almost all pancreatic cancers happens in the K-ras gene, but researchers have been unable to target K-ras despite multiple approaches.

Merchant and his research team have a new strategy to overcome K-ras resistance by targeting MEK and CDK 4/6 proteins that are abnormally activated when there is a mutation in K-ras. Preliminary research indicates that treating pancreas cancers with drugs that block both CDK 4/6 and MEK is highly effective and well-tolerated in mouse models. By combining inhibitors of MEK and CDK 4/6, mouse model survival rates increased by 400 percent.

While original mouse model findings are compelling, Merchant warned that the effect might be different in humans. So, the team will take samples of human pancreas cancers that have been removed from patients, determine the genetic abnormality and implant them into mice. These human tumors will then be treated with drugs targeting CDK 4/6 and MEK.

“We will determine which genetic abnormalities within the tumor correspond to the best response to this therapy. In this way, we can begin to identify molecular signatures in tumors that result in the best responses to this therapy,” Merchant said.

Because this drug combination has already been tried in humans with other types of cancers, if results from the mouse model study are as expected, Merchant thinks that it could also be tested rapidly in human patients with pancreas cancers.

“We hope that within the next two to three years we can transition this targeted therapy into clinical trials,” Merchant said.

In addition to his grant from PANCAN, Merchant has been appointed to the organization’s Scientific and Medical Advisory Board, which provides scientific and clinical expertise to guide PANCAN in planning and implementing research initiatives, information and education services for patients, their families and caregivers, and health care professionals. It is composed of leading cancer scientists, clinicians and health care professionals from institutions across the United States who specialize in pancreatic cancer.

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