Making new strides in their ongoing effort to understand mechanisms behind the relentless growth of cancer cells, researchers at Dartmouth Medical School have found a promising key that may open doors to future treatments in pancreatic and other forms of cancer.
The innovation lies in manipulating an overabundance of chemo-resistant molecules in pancreatic cancer that inactivate pathways that would normally suppress cell growth.
Published in the June 10 issue of the Journal of Biological Chemistry, the study was led by Dr. Murray Korc, a pioneer in early research on growth factor receptors in pancreatic cancer, and chair of the department of medicine at Dartmouth Medical School (DMS) and Dartmouth-Hitchcock Medical Center, and a member of the Norris Cotton Cancer Center. His team's research has focused on suppressing pancreatic tumor growth by determining the mechanisms that enable the cells to grow so quickly.
"Pancreatic cancer is an incredibly resilient and aggressive disease," said Korc. "It grows quickly without causing symptoms, is resistant to chemotherapy, has a strong tendency to metastasize, and patients are often beyond surgery when it is diagnosed."
This study builds on the team's prior research on a molecule called Smad7, found in half of all human pancreatic cancers. Smad7 lies in pathways that normally play an important role in regulating cell growth and often prevents cells when proliferating too quickly. But Smad7 interferes with these pathways that are normally regulated by TGF-beta molecules, so they cannot regulate the growth of cells, and these cells continue to grow unchecked until they eventually become tumors.
"Previously, we found that Smad7 blocks the ability of TGF-beta to inhibit the growth of these cancer cells," said study co-author Dr. Nichole Boyer Arnold, a postdoctoral fellow at DMS and a member of the Norris Cotton Cancer Center. "In this study, we discovered that Smad7 is able to do this by suppressing the function of the retinoblastoma (RB) protein." The RB protein is crucial to empowering TGF-beta to control cell growth.