Chronic Stress and Obesity Fuel Pancreatic Cancer Development

A new study led by UCLA investigators suggests that chronic stress and an unhealthy diet may work together to fuel the early development of pancreatic cancer, shedding light on how lifestyle factors contribute to one of the deadliest malignancies.

In preclinical models, researchers identified a key molecular mechanism by which stress and obesity trigger changes in pancreatic cells that may lead to cancer. Specifically, stress-related neurotransmitters and obesity-related hormones were found to activate a protein called CREB, which is linked to cancer cell growth, through different biological pathways. Stress hormones activate the β-adrenergic receptor/PKA pathway, while obesity-related signals mainly use the PKD pathway. This suggests that both stress and obesity can fuel pancreatic cancer growth through similar mechanisms.

In mouse experiments, a high-fat diet alone led to the growth of precancerous pancreatic lesions. However, when the mice also experienced social isolation stress, they developed even more advanced lesions.

The study also found that social isolation had a stronger impact on cancer development in female mice compared to male mice. The researchers hypothesize that women’s biological response to stress, possibly influenced by estrogen and increased β-adrenergic receptor activity, may make them more susceptible to stress-related cancer risks.

Impact

The findings suggest that stress hormones and obesity-related hormones activate key cancer-promoting pathways, potentially accelerating the onset of pancreatic cancer. One possible solution, researchers suggest, is to explore the use of existing medications to reduce this risk. Since β-adrenergic receptors play a crucial role in stress-related cancer growth, commonly used beta-blockers, which are drugs prescribed for high blood pressure, could be repurposed to help mitigate these effects.

Reference: Sun X, Teper Y, Sinnett-Smith J, et al. Stress and obesity signaling converge on CREB phosphorylation to promote pancreatic cancer. Mol Cancer Res. 2025;23(3):236-249. doi: 10.1158/1541-7786.MCR-24-0785

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