Houston Daily

Researchers at the University of Houston have reported a new potential approach to treat muscle wasting, a common and severe complication in pancreatic cancer patients. Their findings were published in EMBO Molecular Medicine by a team from the UH College of Pharmacy.

Cancer cachexia, which is marked by significant loss of skeletal muscle mass, affects between 60% and 85% of individuals diagnosed with pancreatic cancer. The research led by Ashok Kumar, Else and Philip Hargrove Endowed Professor of Drug Discovery and director of The Institute for Muscle Biology and Cachexia at UH, focused on the IRE1α/XBP1 cellular pathway.

“We show that the IRE1α/XBP1 pathway is a key contributor to muscle wasting,” said Kumar. “Skeletal muscle-specific deletion of the XBP1 transcription factor significantly attenuates pancreatic tumor-induced muscle deterioration.” Aniket Joshi, a post-doctoral fellow in Kumar’s lab, was the first author on the article.

The study explained that this pathway functions within the endoplasmic reticulum, an area in cells where proteins and fats are produced. In pancreatic cancer cases, increased protein breakdown and decreased protein creation result in overall muscle loss.

“Our results also show that the IRE1α/XBP1 axis regulates multiple mechanisms that have a causative role in skeletal muscle wasting. Future studies will determine whether similar mechanisms are involved in muscle wasting in other models of cancer cachexia and pancreatic cancer patients,” said Kumar.

Kumar also noted that these pathways might impact tumor growth, disease progression, and how tumors respond to chemotherapy. “The role of this pathway in the regulation of pancreatic cancer cell survival, especially in response to chemotherapeutic agents, needs further investigation,” he said.