Breakthrough Discovery Links Stress, Inflammation to Aggressive Pancreatic Cancer
A new study from University of California San Diego School of Medicine has uncovered a critical link between cellular stress, inflammation, and the progression of pancreatic ductal adenocarcinoma (PDAC), offering potential for earlier detection and more effective treatment of this deadly cancer. The findings, published in Cell Reports in July 2025, identify a specific biological pathway that could serve as an “early warning system” for the disease.
Researchers have long known that inflammation and cellular stress play a role in cancer development, but the precise mechanisms have remained elusive. Previous research demonstrated that these factors activate a protein called STAT3 – short for signal transducer and activator of transcription 3 – in pancreas cells, fueling tumor growth and resistance to therapy. This new study illuminates how STAT3 drives these processes.
STAT3 and the Integrin β3 Connection
The research team discovered that in certain cancer cells, STAT3 activates a gene known as Integrin β3 (ITGB3) when exposed to inflammatory proteins and low oxygen conditions. “This activation of ITGB3 is a key driver of pancreatic cancer initiation and progression,” a senior author stated.
Specifically, the study revealed several crucial findings:
- ITGB3 expression directly promoted the development and accelerated the growth of PDAC tumors.
- Even cellular stress induced by chemotherapy triggered STAT3 activation, subsequently increasing ITGB3 expression in PDAC cells.
- Blocking the STAT3 pathway, which regulates ITGB3, significantly delayed tumor initiation.
- STAT3 influences the expression of 10 genes, including ITGB3, forming a unique “STRESS” signature.
The “STRESS” Signature: A Predictive Tool for Pancreatic Cancer
This newly identified “STRESS” signature represents a significant advancement in cancer diagnostics. Researchers found that it outperformed existing gene signatures in predicting both the likelihood of a patient developing pancreatic cancer and the aggressiveness of the tumor. “The STRESS signature better predicted not only whether cells would later develop into full-blown pancreatic cancer, but also predicted the aggressive state of the tumor,” researchers noted.
The implications for precision medicine are substantial. The ability to identify precancerous cells through this signature could lead to earlier interventions and improved patient outcomes. Clinicians could potentially use the STRESS signature to determine which patients are at highest risk of developing aggressive cancers and tailor treatment plans accordingly.
Expanding the Scope: Targeting Inflammation in Multiple Cancers
The research extends beyond pancreatic cancer. The team is now investigating molecules that can block inflammation from activating ITGB3, not only in PDAC but also in other cancers affecting tissue surfaces, including lung, breast, and skin cancers. The goal is to prevent tumor progression, metastasis, and drug resistance.
David Cheresh, Ph.D., distinguished professor and vice chair for research and development in the Department of Pathology at UC San Diego School of Medicine and a member of UC San Diego Moores Cancer Center, believes these findings represent a crucial step forward in the fight against cancer. The research offers a promising new avenue for early detection, personalized treatment, and ultimately, improved survival rates for patients battling this devastating disease.
Source: University of California – San Diego
Journal reference: Campos, A. D., et al. (2025). A STAT3/integrin axis accelerates pancreatic cancer initiation and progression. Cell Reports. doi.org/10.1016/j.celrep.2025.116010.
