Posted on 06/23/2022 6:59:37 PM PDT by ConservativeMind
Calcium channel blockers may improve treatment for pancreatic cancer patients receiving gemcitabine-based chemotherapy.
"These exciting data suggest that the addition of a calcium channel blocker to gemcitabine may have some benefits, especially since calcium channel blockers have a very favorable toxicity profile, are low cost and are readily available," said Thao Pham, Ph.D.
Pancreatic cancer generally has poor survival rates due in part to resistance to chemotherapy. While palliative chemotherapy can improve patients' symptoms and overall quality of life, more effective treatment options are desperately needed.
In the study, the investigators sought to identify new treatment strategies to prevent or overcome resistance to gemcitabine, one of the most widely used pancreatic cancer drugs.
Using RNA sequencing and proteomic analysis to study pancreatic cell lines treated with gemcitabine, the team discovered a subset of gemcitabine-resistant tumor cells with enhanced calcium-dependent calmodulin signaling. Calmodulin, a calcium-binding messenger protein, is known to promote expression of the oncogene KRAS, which is among the most commonly mutated oncogenes found in pancreatic tumors.
They discovered that pharmacologically inhibiting calcium-dependent calmodulin activation in pancreatic cancer cell lines decreased drug-resistant phenotypes. Additional single-cell RNA sequencing identified that this was due to impaired activation of the RAS/ERK signaling pathway.
Using calcium channel blocker drugs, such as amlodipine, in vitro and in orthotopic xenografts and transgenic mouse models of pancreatic cancer treated with gemcitabine, the investigators were able to inhibit RAS/ERK signaling, suggesting an enhanced therapeutic response to gemcitabine.
The findings suggest that calcium-dependent calmodulin signaling is a protective mechanism used by pancreatic cancer cells in response to gemcitabine treatment and that calcium channel blockers may provide clinical benefit to patients.
"Next steps include a randomized clinical trial investigating whether adding calcium channel blockers such as amlodipine or nifedipine can help extend survival for patients receiving gemcitabine treatment," Pham said.
(Excerpt) Read more at medicalxpress.com ...
It is a preferred blood pressure medicine, along with ARBs.
Something to keep in mind.
Calcium channel blockers made my legs swell near my ankles. I was switched to lisinopril and a water pill. This was several years ago.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.