Pancreatic Cancer Discovery Opens the Door for New Treatments

Pancreatic cancer is tricky to manage because it spreads easily and early, and the tumors have a unique biological makeup. But, researchers made a breakthrough by learning about the genetic changes that occur during tumor migration — and also found a drug that can obstruct the process.

The five-year survival rate for pancreatic cancer is only 12 percent, which is a slight increase in 2023 compared to previous years.

The number of cases is rising worldwide, however, and by 2030, pancreatic cancer is predicted to be the second leading cause of cancer deaths.

In 85 percent of patients, the cancer has already spread outside of the pancreas at diagnosis.

Even when the cancer is localized to the pancreas and surgical removal is possible, the majority of patients face a recurrence of their cancer.

The metastasis causes these patients to eventually succumb to the disease, which is why researchers are focused on understanding the biology of metastatic pancreatic cancer.

Second, although pancreatic cancer cells do not have to travel far to reach the liver, along the way they genetically reprogram themselves and become stronger.

The result: newly seeded cancer cells in the liver have a distinctly different biology from the primary tumor in the pancreas, and are able to resist standard treatment, Carpizo said.

In their latest work, Wilmot researchers built on what was already known about a key gene, Netrin-1, involved in pancreas, breast and colon cancers.

They discovered, for the first time, the complex mechanisms that allow Netrin-1 to drive the lethal, genetic changes as pancreatic cancer cells migrate to the liver.

They also showed how Netrin-1 activates hepatic stellate cells, which are involved in liver fibrosis, a serious chronic disease, priming the liver as a host for cancer.

In mice and in tissue studies, when researchers suppressed Netrin-1 with the anti-cancer drug (NP137), cancer was less likely to spread and cancer cell death occurred.

He noted that NP137 is made by Netris Pharma, of Lyon, France, and is currently being tested in clinical trials in that country.

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Sources:

Crissy Dudgeon, Anthony Casabianca, Chris Harris, Charline Ogier, Mélanie Bellina, Stephany Fiore, Agnes Bernet, Benjamin Ducarouoge, David Goldschneider, Xiaoyang Su, Jason Pitarresi, Aram Hezel, Subhajyoti De, Wade Narrow, Fady Soliman, Cory Shields, Debora Barbosa Vendramini-Costa, Orjola Prela, Lan Wang, Igor Astsaturov, Patrick Mehlen, Darren R. Carpizo. Netrin-1 feedforward mechanism promotes pancreatic cancer liver metastasis via hepatic stellate cell activation, retinoid, and ELF3 signaling. Cell Reports, 2023; 42 (11): 113369 DOI: 10.1016/j.celrep.2023.113369

University of Rochester Medical Center. “Pancreatic cancer discovery opens the door for new clinical trial.” ScienceDaily. ScienceDaily, 16 November 2023. <www.sciencedaily.com/releases/2023/11/231116140835.htm>.

Materials provided by University of Rochester Medical Center. Original written by Leslie Orr. Note: Content may be edited for style and length.

Images from:

Photo by Anna Tarazevich

https://www.pexels.com/photo/pancreatic-cancer-spelled-with-scrabble-tiles-8428394/