HIGHLIGHTS
- HNF1A was identified as a potential driver of pancreatic cancer metastasis
- FGFR4 was shown to play a key role in cancer cell migration and invasion
- Findings suggest treatment with an FGFR4 inhibitor can disrupt tumor spread
Findings suggest a strategy for slowing cancer spread using existing drugs
Researchers at Roswell Park Comprehensive Cancer Center have uncovered new evidence on how pancreatic cancer spreads. In a new study in the journal Molecular Cancer, the team describes how a protein called HNF1A may help drive metastasis — the process by which cancer spreads to other parts of the body — and highlights another protein, FGFR4, as a potential target for future therapies.
Pancreatic cancer is one of the most aggressive and deadly cancers, with a five-year survival rate of 13.3%. Most patients are diagnosed at a late stage, when the cancer has already spread and treatment options are limited. Metastatic pancreatic cancer is especially difficult to treat, and current therapies often offer only modest benefits.
A Roswell Park team led by Ethan Abel, PhD, reports that HNF1A, a transcription factor that regulates gene expression, appears to play a role in making cancer cells more mobile and, therefore, more dangerous.
“We uncovered a novel role for the oncogenic transcription factor HNF1A in driving pancreatic cancer metastasis — a hallmark of this aggressive and hard-to-treat cancer,” says Dr. Abel. “Through our preclinical work in the lab, we also identified the growth factor receptor FGFR4 as a critical mediator of HNF1A-driven metastasis, and demonstrated that targeting FGFR4 with clinically viable inhibitors can limit tumor spread.”
The study’s first author, Katherine Gatsos, PhD, a postdoctoral fellow in Dr. Abel’s lab, helped lead the research that uncovered this HNF1A–FGFR4 connection. The team showed that blocking FGFR4 reduced the ability of cancer cells to spread — a promising finding that could inform future treatment strategies.
“These findings not only identify a novel role for HNF1A in the malignancy of pancreatic cancer,” Dr. Abel notes, “but also identify a strategy that might be used to slow or prevent metastasis in people with this disease.”
While more research is needed before these findings can be translated into patient care, the study adds to growing efforts to understand the biology of pancreatic cancer and develop more effective treatments — especially for patients facing metastatic disease.
This work was supported by Roswell Park Comprehensive Cancer Center and by grants from the National Cancer Institute (grants P30CA01605, R37CA275961, R01CA279713, CA267467 and CA211878), PanCAN (the Pancreatic Cancer Action Network-AACR Pathway to Leadership Grant), the SAS Foundation for Cancer Research; the Roswell Park Alliance Foundation, and the Hirshberg Foundation for Pancreatic Cancer Research. The authors also acknowledge with appreciation their access to data provided by the Ontario Institute for Cancer Research.
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