Deadly cancer cells have learned to "help each other" in order to survive

Tumor cells in the most common forms of pancreatic cancer share nutrients during survival and growth
.
Biologists at the University of California, Irvine and their collaborators have discovered a new finding in a 4-year survey that may help better treat pancreatic ductal adenocarcinoma, which accounts for more than
90 percent of pancreatic cancer cases.
The scientists' paper was published in
the journal Nature Cancer.
Although pancreatic cancer is relatively rare, it is one of
the leading causes of cancer death in the United States.

One obstacle to treating pancreatic ductal adenocarcinoma (PDA) is that it usually does not show early symptoms
.
Another obstacle is its density and complexity of fibrous tumors
.
As a result, they do not have fully functioning blood vessels
in the tumor.
On the one hand, this makes effective chemotherapy difficult to administer.

However, this also means that the tumor has developed a different metabolism
.

"Without blood vessels, PDA cells can't get the normal nutrients they need, so they come up with other ways to nourish themselves and grow," said Christopher Halbrook, assistant professor of molecular biology and biochemistry and principal and co-corresponding author
.
Understanding this process is critical
to designing treatments that target cancer metabolism.

The researchers found that there are two different types of PDA cancer cells in the tumors, each with a different metabolic process
.
"This different program allows them to exchange nutrients, so each animal gets what it needs
," Halbrook said.

The team found that one class of cells was susceptible to mitochondrial toxins, which are commonly used in cancer treatment, but that survived with the help of asparagine amino acids obtained from another class of cells
.
The latter have plenty of asparagine to share, as they overproduce asparagine
under constant stress.

"After learning this, we found that we could use asparaginase to reconstruct a tumor's vulnerability to mitochondrial toxins," Halbrook said
.
The team's findings provide important insights
into improving the treatment of pancreatic cancer and the treatment of other diseases.
Halbrook said: "For tumors, we cannot assume that there is a single weakness
.
If we are going to perform metabolism-based treatments, targeting multiple cellular behaviors will be critical
.
"The scientists validated the metabolic symbiosis model
by sequencing cloned human and mouse PDA tumor cells and single-cell RNA.
Then using preclinical models, they made another important discovery
.

"When we treated tumors with Phenformin, a potent mitochondrial toxin, and asparaginase, it stopped the tumor from growing," Halbrook said
.
He added that there is more to learn, including identifying the cause of persistent stress in the supporting cells that drive the
symbiosis.