Karmanos researchers contribute cover design, research story in February issue of “Gastroenterology”
Tuesday, January 08, 2013
Ramzi Mohammad, Ph.D., professor of Oncology at the Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine (WSU SOM) and Asfar Azmi, Ph.D., research scientist in the Pathology Department at WSU SOM, have contributed the cover design of the February edition of “Gastroenterology.” The pair, along with their co-authors, also has an article in the print publication, titled, “Selective Inhibitors of Nuclear Export Block Pancreatic Cancer Cell Proliferation and Reduce Tumor Growth in Mice.”
The cover image is a visual illustration of the team’s research into the role that tumor suppressor proteins (TSPs) play in preventing the growth of pancreatic cancer cells, as well as the identification of a cellular protein, Exportin-1 (XPO-1 or CRM-1), which inhibits certain tumor suppressor functions. CRM-1 is over-expressed in pancreatic cancer, making it an attractive therapeutic target. CRM-1 shuttles tumor suppressor proteins out of the nucleus of the cell and into the cytoplasm, which surrounds the nucleus. Those suppressor proteins work only when they are inside the nucleus, so CRM-1 actions make the tumor-killing drugs less effective and allow tumors to continue growing.
The authors, in collaboration with Karyopharm Therapeutics of Boston, have developed selective inhibitors of nuclear export that bind to CRM-1 and block the export of TSPs, resulting in tumor shrinkage of pancreas tumors in mice. Researchers note that treatment of pancreatic cancer is an unmet clinical problem with annual deaths that exceed breast and prostate cancers, due to the lack of effective drug therapies. Targeting CRM-1 forces the tumor suppressor proteins to function properly and induce cancer-specific cell death.
The research team, in collaboration with Philip A. Philip, M.D., Ph.D., F.R.C.P., leader of the Gastrointestinal and Neuroendocrine Oncology Multidisciplinary Team at Karmanos and WSU SOM, and Anthony F. Shields, M.D., Ph.D., associate center director of Clinical Sciences at Karmanos and WSU SOM, are initiating gastrointestinal clinical trials at Karmanos using this novel inhibitor starting in February.
We congratulate the team on the publication of their research and their artistic contributions to this high impact journal!