JAN 21, 2017 09:18 AM PST

The Cues that Tell Pancreatic Cancer to Steal

WRITTEN BY: Xuan Pham

Acting like cunning thieves in the night, pancreatic cancer can hack into their microenvironment to selfishly steal the essential nutrients for its own survival. A new study highlights the mechanisms behind this process, and points to a promising drug candidate that may prevent theft of the nutrients.

Tumor (green), stromal cells (red) | Image: Salk Institute"Pancreatic cancer is a deadly disease and is very understudied when it comes to how it communicates with the microenvironment," said Ronald Evans, director of Salk's Gene Expression Laboratory, and the study’s senior author. "Our findings open up a lot of avenues for future study."

Indeed, scientists have shown that the stromal microenvironment, made up of fat and connective cells that provide structural support for tissues and organs, plays a big role in supporting tumor growth. But exactly how this happens remained a complex mystery.

To understand how tumors hack into this microenvironment, researchers at the Salk Institute replicated this biological process with and without signaling chemicals from the pancreatic stroma. "We worked out a culture system so that we could grow human pancreatic cells in a three-dimensional system in both the presence and absense of stromal signals," said Mara Sherman, the study’s first author.

The team showed that tumors relied on stromal molecules to mobilize their entire metabolic process. In essence, signaling molecules trigger the tumors to accelerate their growth and overall metabolism. At the epigenetic level, the tumors had increased histone acetylation at transcriptionally enhanced genes, which suggests a deeper level of genetic alteration.

"The tumor is essentially hacking into that stromal microenvironment and grabbing what it needs to up its metabolism," said Michael Downes, one of the study’s co-authors.

The Salk team hypothesized that changes at the epigenetic level implicates the pancreatic cancer epigenome as a therapeutic target. That is, blocking the signals at the epigenetic level may prevent the tumor cells from hacking into its microenvironment.

To test this hypothesis, the team administered an epigenetic inhibitor known as JQ1 into their cancer models. In cells, the drug blocked the stromal signals and reversed the genetic changes associated with increased metabolism. In a mouse model, the drug slowed tumor progression significantly.

The team plans to follow-up this pathway with JQ1 and other inhibitors to understand whether it will be effective in humans. Of note, pancreatic cancer is notorious for its lethality. Only about 25 percent of patients survive past the one-year mark from diagnosis. Thus, any insight that can be translated into drug therapies offers huge hope for patients. 

Additional sources: Salk Institute 

About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
You May Also Like
OCT 19, 2019
Cancer
OCT 19, 2019
The risks of an inflammatory diet
New research published recently in Nutrients highlights the detriments that an inflammatory diet can have on increasing the risk of certain types of breast...
OCT 19, 2019
Health & Medicine
OCT 19, 2019
Does Cuttlefish Ink Hold a Cure for Cancer?
Using nanoparticles to deliver cancer-fighting compounds directly into tumors has been a hot research topic for the past few years. According to Lisa Ayga...
OCT 19, 2019
Drug Discovery & Development
OCT 19, 2019
Treating Drug-Resistant Acute Lymphoblastic Leukemia
New therapeutics may have helped improve survival rates for acute lymphoblastic leukemia patients but some patients still remain unresponsive to existing t...
OCT 19, 2019
Drug Discovery & Development
OCT 19, 2019
Comparison of Three Frontline Breast Cancer Drugs
Breast cancer affects 250,000 women in the U.S. annually. Those with most common form test positive for hormone receptors (HR+) and negative for the HER2 r...
OCT 19, 2019
Drug Discovery & Development
OCT 19, 2019
Compound in Daffodils Can Help Fight Cancer
Preventing the growth of tumors presents a challenge for scientists in finding a cure to cancer. Now however, researchers from the University Libre de Brux...
OCT 19, 2019
Cancer
OCT 19, 2019
Using temperature to awaken immune response to fight brain cancer
Glioblastoma is the most common form of adult brain cancer and also one of the most aggressive human cancers. Immunotherapy has yet to be shown proven effe...
Loading Comments...