In a significant breakthrough published in Molecular Cancer, researchers from National Chung Cheng University (CCU) and National Cheng Kung University (NCKU) have identified a novel TIMP1-CD63 signaling mechanism that allows KRAS-mutated pancreatic cancer cells to escape immune detection. With KRAS mutations present in approximately 90% of pancreatic cancer patients, this discovery offers promising new avenues for targeted treatment strategies.
Led by CCU’s Chair Professor Tsai Shaw-jenq and NCKU’s College of Medicine Dean Shan Yan-shen, the study combined in vitro and in vivo mouse experiments with spatial transcriptomic analysis of tumor samples. The researchers also discovered that a deficiency in the gene dual-specificity phosphatase-2 (DUSP2) further promotes unchecked tumor growth. Together, the active TIMP1-CD63 signaling and low DUSP2 levels create a self-sustaining “vicious cycle” that drives cancer progression.
"Disruption of the vicious cycle, maybe a highly potential way to inhibit pancreatic cancer progression," the researchers commented, highlighting the potential of this pathway as a therapeutic target.
The findings also shed light on the role of chronic inflammation, specifically the increased presence of macrophages, in maintaining the tumor microenvironment that favors cancer progression.
Funded by Taiwan’s National Science and Technology Council and National Health Research Institutes, this study not only deepens our understanding of pancreatic cancer biology but also paves the way for developing novel intervention strategies that could improve patient outcomes.
