APR 08, 2020 1:57 PM PDT

Changing cell pH to block pancreatic cancer

New research published in Cancer Discovery suggests that manipulating the pH of pancreatic cancer cells can deter cell growth. The study was conducted by scientists at Sanford Burnham Prebys.

"Pancreatic cancer is predicted to soon become the second-leading cause of cancer-related deaths in the U.S.," says Cosimo Commisso, Ph.D., an assistant professor in Sanford Burnham Prebys' NCI-designated Cancer Center. "Given that the five-year survival rate for people newly diagnosed is less than 10%, it's crystal clear that we need better therapies--and finding new cancer targets can help us tailor treatments and possibly save the lives of many more patients."

The researchers were interested in a particular ion transport protein, known as NHE7. "Our study suggests that interfering with cellular pH represents a new therapeutic avenue to treat pancreatic cancer, one of the deadliest cancers for which there is currently no effective treatment," says Commisso. "We have shown that a sodium-hydrogen exchanger called NHE7 plays a significant role in pancreatic tumors, and by suppressing it, we can promote cancer cell death."

The idea is to deplete NHE7 to the point that the pH within a cancer cell is disrupted and its metabolic pathways are affected. NHE7 is crucial for transporting ions, exchanging hydrogen ions with sodium ions in order to keep internal cell pH equilibrium. This protein is especially important for cancer cells, which because of their overactive metabolism, overproduce acid that must be eliminated from the cell. But…thought the researchers…if NHE7 isn’t there to do its job…

"We hypothesized that the increased acid production that occurs in tumor cells could be harnessed as a therapeutic vulnerability, so we looked for a strategy to specifically target this," says first author Koen Galenkamp, Ph.D. "By mining a number of pancreatic cancer databases, we found that NHE7 levels were higher in tumors compared to normal pancreas, and highest in the tumors of patients with the poorest prognoses. This led us to test if we could make pancreatic cells vulnerable by disabling or eliminating NHE7 to undermine the alkaline cytoplasmic pH they require to stay fit."

Photo: Pixabay

Their findings concluded that suppressing NHE7 successfully lowers the pH of the cell's cytoplasm, resulting in apoptosis. They also showed that suppressing NHE7 in mice with human tumors caused tumors to shrink or completely halt growth.

Commisso adds, "This study illustrates the potential to target pH balance as an approach to combat pancreatic cancer. Our next step is to work with the Conrad Prebys Center for Chemical Genomics--the drug discovery facility at our Institute--to find ways to disable NHE7 and limit the Golgi's ability to sequester acid. If successful, cancer cells would be unable to maintain the proper pH that they need to grow."

Sources: Cancer Discovery, Eureka Alert

About the Author
  • Kathryn is a curious world-traveller interested in the intersection between nature, culture, history, and people. She has worked for environmental education non-profits and is a Spanish/English interpreter.
You May Also Like
SEP 18, 2020
Cancer
Itraconazole: the key is in the dosage
SEP 18, 2020
Itraconazole: the key is in the dosage
Precision medicine specific to a patient’s genetics or immune system is spearheading new paths of cancer treatment ...
OCT 20, 2020
Clinical & Molecular DX
Non-coding RNA As A Barometer For Liver Health
OCT 20, 2020
Non-coding RNA As A Barometer For Liver Health
October is liver cancer awareness month — a month dedicated to educating people about the risk factors and prevent ...
OCT 18, 2020
Microbiology
Mouth Microbes Play a Role in Oral Cancer Development
OCT 18, 2020
Mouth Microbes Play a Role in Oral Cancer Development
Oral hygiene is not only important for keeping teeth and gums healthy; it can also affect a person's health in general.
NOV 09, 2020
Cancer
A Prognostic Expression Profile for Osteosarcoma
NOV 09, 2020
A Prognostic Expression Profile for Osteosarcoma
Tireless research goes into every cancer diagnostic tools and new therapy. Many types of cancer have made giant steps fo ...
NOV 12, 2020
Immunology
Anti-bodies against a sugar present in meat and dairy products can increase the risk of Colorectal Cancer
NOV 12, 2020
Anti-bodies against a sugar present in meat and dairy products can increase the risk of Colorectal Cancer
Nutrition is essential to health; what we eat in our daily diet affects our overall health condition and what diseases w ...
DEC 01, 2020
Cancer
The price tag of prostate cancer treatment
DEC 01, 2020
The price tag of prostate cancer treatment
New research published in The Journal of Urology from the Official Journal of the American Urological Association&n ...
Loading Comments...