Pancreatic Cancer Doesn't Just Grow - It Rewires its Surroundings to Spread Fast, and Scientists May Have Found a Way to Stop It

A recent Brazilian study in Molecular and Cellular Endocrinology reveals how pancreatic cancer spreads early on. It shows the protein periostin, working with pancreatic stellate cells, enables cancer to invade nearby nerves. This initial nerve infiltration boosts metastasis risk and drives disease aggressiveness, pointing to promising targets for targeted, personalized therapies. 

Pancreatic tumors never operate alone — they reprogram surrounding healthy tissue to aid cancer invasion, explaining why the disease is so hard to stop once it spreads. The most common type, pancreatic adenocarcinoma, arises in juice-producing glandular cells and makes up about 90% of all pancreatic diagnoses. 

Globally, it ends around 510,000 lives annually. In Brazil, the National Cancer Institute (INCA) estimates 11,000 new diagnoses and 13,000 deaths yearly. "It's an aggressive cancer that's difficult to treat. Around 10% of patients have a chance of long-term survival, such as five years after diagnosis," notes study co-author and oncologist Pedro Luiz Serrano Uson Jr. 

Pancreatic cancer’s lethality stems partly from perineural invasion, where tumor cells infiltrate and travel along nerves – causing intense pain and providing highways for metastasis. “Perineural invasion signals cancer aggressiveness," Uson explains, as nerves link distant body regions, easing tumor spread.

Mapping the Tumor’s Hidden support system.

Conducted at the Center For Research on inflammatory diseases (CRID)- a FAPESP research, innovation, and Dissemination Center (RIDC) - the study was led by Carlos Alberto de Carvalho Fraga under principal investigator Helder Nakaya. Nakaya also works as a senior researcher at Einstein Israelite Hospital and professor at the University of São Paulo's School of Pharmaceutical Sciences. 

To decode nerve invasion , the team deployed cutting-edge tools to profile thousands of genes in single cells while pinpointing their positions in tumor tissue. “We integrated data from dozens of samples at unprecedented resolution,” Nakaya notes. 

The evolving tumor microenvironment sparks a desmoplastic reaction, piling up dense fibrous tissue – packed with cells and proteins – that stiffens and inflames the area. This barrier blocks chemotherapy and immunotherapy from reaching the tumor, shielding cancer cells to survive and spread. “That’s why pancreatic cancer remains so hard to treat,” Uson says.

Promising Targets

Despite these challenges, the researchers view periostin as a promising target for future treatments. Dialing down its activity or removing the stellate cells that produce it could help limit nerve invasion and slow down the cancer spread. "This work points to paths that may guide future approaches to treating pancreatic cancer," Nakaya says.

This Brazilian breakthrough from CRID demystifies pancreatic cancer’s early perineural invasion, pinpointing periostin and stellate cells as key enablers that reprogram the microenvironment – triggering desmoplasia to shield tumors from therapies and fuel relentless spread. With global deaths matching 510,000 yearly diagnoses and Brazil’s stark 11,000-13,000 burden alongside ~10% five-year survival, these revelations underscore why this adenocarcinoma dominates as an untreatable killer. 

By exposing the tumor’s “hidden support system” via single-cell genomics, the study opens doors to targeted interventions:periostin inhibitors to halt nerve hijacking, stroma-softening agents to enhance drug delivery, and personalized strategies blending these with immunotherapies. Urgent clinical trials could elevate survival rates, transforming a disease of near-certain fatality into one of viable hope.