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Lorazepam Has Negative Impact on Survival in Pancreatic Cancer

Alprazolam reduced IL-6 in human pancreatic cancer-associated fibroblasts and was associated with improved progression-free survival

By Elana Gotkine HealthDay Reporter

TUESDAY, Aug. 22, 2023 (HealthDay News) — Lorazepam stimulates fibrosis and inflammatory signaling and is associated with reduced survival in patients with pancreatic cancer, according to a study published online Aug. 17 in Clinical Cancer Research.

Abigail C. Cornwell, from the Roswell Park Comprehensive Cancer Center in Buffalo, New York, and colleagues examined the association between benzodiazepines (BZD) and pancreatic cancer patient survival outcomes. The impact of lorazepam was examined in the murine pancreatic adenocarcinoma tumor microenvironment. Furthermore, the impact of BZDs was examined on interleukin (IL)-6 expression or secretion by human-immortalized pancreatic cancer-associated fibroblasts (CAFs).

The researchers found that in pancreatic cancer patients receiving chemotherapy, lorazepam was associated with worse progression-free survival (PFS), while alprazolam was associated with improved PFS. Desmoplasia (fibrosis and extracellular matrix protein deposition), inflammatory signaling, and ischemic necrosis were promoted by lorazepam. Preferential expression of GPR68 was seen on human pancreatic ductal adenocardinoma CAFs, and n-unsubstituted BZDs, including lorazepam, significantly increased IL-6 expression and secretion in a pH and GPR68-dependent manner. In contrast, IL-6 was reduced in human CAFs in a pH and GPR68-independent manner by alprazolam and other GPR68 n-substituted BZDs. Relative to alprazolam and patients not receiving BZDs, lorazepam was associated with worse survival outcomes across many cancer types.

“We think the mechanism comes down to a difference in structure between different benzodiazepines,” coauthor Michael Feigin, Ph.D., also of the Roswell Park Comprehensive Cancer Center, said in a statement. “Alprazolam has the opposite effect as lorazepam; it has no impact on GPR68, but it potently decreases IL-6, and we think this decreases the inflammatory potential of these tumors.”

One author disclosed ties to the pharmaceutical industry.

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