An enzyme known as MICAL2 has been found to enhance tumor growth and spread in the most prevalent type of pancreatic cancer, as revealed by a recent study.
Pancreatic cancer results in approximately 50,000 deaths annually, as reported by the National Cancer Institute, and there are limited effective treatments available for this illness. A new study from researchers at the University of California San Diego School of Medicine indicates that MICAL2, an enzyme, fosters tumor growth and metastasis in pancreatic ductal adenocarcinomas (PDAC), which is the most common type of pancreatic cancer. This study is set to be published on January 2, 2025, in Cancer Research, a journal affiliated with the American Association for Cancer Research.
Typically, MICAL2 is vital for cell movement and structure. However, when the scientists analyzed gene expression in PDAC tumor cells, they discovered an unusually high production of this enzyme in comparison to healthy cells—marking the first experimental connection between MICAL2 and pancreatic cancer.
Additionally, the research uncovered several key points:
- Among patients who had surgery to remove their PDAC tumors, those with lower levels of MICAL2 in their tumor cells lived approximately twice as long as those with higher levels, indicating that MICAL2 may be linked to the disease advancing to a more severe stage.
- MICAL2 seems to enhance the KRAS signaling pathway, which governs cell growth, multiplication, and death; this pathway is known to be the primary force behind pancreatic tumor development and the spread of cancer to other body tissues. When the MICAL2 gene was silenced in PDAC cells, the activity of the KRAS signaling pathway was significantly reduced.
- When tumor cells lack sufficient MICAL2, the KRAS signaling pathway cannot absorb the nutrients necessary for tumor growth.
- MICAL2 expression aids in the division, migration, and invasion of tumor cells into healthy tissue.
The research indicates that MICAL2 could be a valuable target for drug therapies aimed at treating PDAC, according to senior author Andrew Lowy, M.D., who is a professor and chief of surgical oncology at UC San Diego School of Medicine and the associate clinical director for surgery at UC San Diego Moores Cancer Center.
“Pancreatic cancer has the highest death rate among commonly occurring cancers, and current treatments fall significantly short,” stated Lowy. “We believe it is feasible to develop drugs targeting MICAL2, as it is an enzyme among proteins that have successfully been inhibited in treatments for other diseases. We are currently working on identifying drug candidates to start the process of blocking MICAL2’s function in pancreatic cancer.”
