- Pancreatic cancer is one of the deadliest forms of cancers.
- Scientists have found that suppressing the GRP78 protein could show new promise in treating pancreatic cancer.
- The new research could emphasize the potential of a promising pancreatic cancer target.
Pancreatic cancer occurs when the cells in the pancreas have the ability to invade other parts of the body. A new research from the Keck School of Medicine of the University of Southern California has shown new promise in the fight against one of the lethal forms of cancer.
The research study in mutated mice showed that expressing only half of the amount of the glucose-regulated protein GRP78 could be enough to halt the development of the earliest stage of pancreatic cancer.
According to the American Cancer Society, more than 53,600 people will be diagnosed with pancreatic cancer and more than 43,000 people will die due to the disease this year.
The research study published in the Proceedings of the National Academy of Sciences, was funded by the National Institutes of Health.
The proteins were required for switching to healthy pancreatic cells that produce enzymes to digest food into the potentially cancerous cells.
This could reduce the amount of the protein that delays the pancreatic cancer development and prolongs survival.
Amy Lee, PhD, professor of biochemistry and molecular medicine at the Keck School and the Judy and Larry Freeman Chair in Basic Science Research at the USC Norris Comprehensive Cancer Center, said, "Cancer cells are addicted to high levels of GRP78 for cancer development and growth. Our hope is that partially reducing or inactivating the protein by therapeutic agents could one day be an effective complementary therapy for pancreatic cancer and other cancers, while sparing other healthy organs."
Protein's Role in Cancer Progression
The human GRP78 gene has been first cloned by Amy Lee, and also investigated the protein's role in cancer progression and treatment. She even received a MERIT award from the National Cancer Institute and was also elected as the fellow of the American Association for the Advancement of Science.
Lee said, "As developing drugs directly targeting the KRAS genetic mutation has been challenging, we are thrilled these findings indicate that we can attack KRAS-driven pancreatic cancer through an entirely new method."
Glucose Regulated Protein 78 (GRP78) protein is a stress-inducible protein which could fold the newly synthesized protein and allows substances in the endoplasmic reticulum.
In times of stress, a fraction of GRP78 is being shipped out of the cell surface to perform growth and survival functions. Cancer cells that survive treatment were found to undergo more stress than the healthy cells. This could result in an increased levels of GRP78 to help the cancer cells survive, grow and develop resistance.
Protein Levels and Cancer Risk
There are a number of studies that show a relationship between highly elevated levels of protein and risk of cancer recurrence or survival.
GRP78 protein could be an effective anti-cancer target and developing potential inhibitors of the protein that could develop possible cancer treatment.
Lee even said that, certain foods like soy and green tea were also found to contain natural compounds that could suppress the protein for cancer treatment.
Lee said, "Translating any basic science discovery into clinical practice is a long process that requires substantial resources."
"But given the notorious difficulties of treating KRAS-mutation related cancers, particularly in a disease as devastating as pancreatic cancer, this research provides hope and a novel approach. I am excited to put our theories to test in the clinical setting."
- Jieli Shena, Dat P. Haa, Genyuan Zhua, Daisy F. Rangela, Agnieszka Kobielaka, Parkash S. Gillb, Susan Groshenc, Louis Dubeaub, and Amy S. Lee,'GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice,' Proceedings of the National Academy of Sciences of the United States of America, (PNAS) 2017; doi: 10.1073/pnas.1616060114