Pancreatic cancer has a grim prognosis. It is usually detected after the disease has spread, and chemotherapy tends to do little to slow the cancer’s growth. Even with treatment, most patients live only about six months after they are diagnosed with the disease.
Researchers in Professor David Tuveson’s laboratory at Cold Spring Harbor Laboratory (CSHL) think it’s possible to do better with a different type of treatment. Part of the problem, they say, is that cancer cells in the pancreas are protected by the dense matrix that surrounds them. The matrix is a mixture of extracellular components and noncancerous cells known as the stroma. All solid tumors contain stroma. In pancreatic cancers, this fibrous material is particularly abundant, making up nearly 90 percent of a tumor’s mass. This stroma impedes anticancer drugs’ from getting to their targets. Additionally, stromal cells secrete factors that actually help the tumors grow.
Overcoming the stroma’s protective influence has been challenging, but new leads from Tuveson’s team, as reported on October 26, 2018 in the journal Cancer Discovery, point to a promising strategy. In fact, the new findings suggest that drugs which target the right cellular pathways can do more than just thwart tumor-supporting cells in the stroma. They may recruit them into the anticancer fight.
A key element of the stroma is a type of cell called a fibroblast. Fibroblasts manufacture the stroma’s connective tissue. They also generate factors that promote cancer cell growth and prevent the immune system from attacking the cancerous cells. Last year Tuveson’s team discovered that the stroma of pancreatic tumors contains at least two types of fibroblasts. One type show features known to support tumor growth, the other type appear to have the opposite effect.
The good news is that the fibroblasts’ identities are not fixed. With the right cues, tumor-promoting fibroblasts can become tumor-restrictors.
“These cells can convert into one another, depending on the cues they get from the microenvironment and from the cancer cells,” explains Giulia Biffi, a postdoctoral researcher in Tuveson’s lab who led the new study. “This is potentially useful because, in theory, you can shift the tumor-promoting cells to tumor-restraining, rather than just depleting the tumor-promoting cells.”
In this new report, Biffi and her colleagues have identified specific molecular signals released by cancer cells that determine fibroblasts’ character within pancreatic tumors. They have discovered that one such molecule, IL-1, drives fibroblasts to take on a tumor-promoting identity. They have also shown how another molecule, TGF-beta, overrides that signal and keeps fibroblasts in a potentially anticancer state even when IL-1 is present.
The researchers are now exploring what happens to pancreatic tumors when they manipulate IL-1 and TGF-beta signaling and convert tumor-promoting fibroblasts to a more beneficial state. They will also investigate what happens when they target these pathways in combination with chemotherapy or cancer immunotherapies. Ultimately, Biffi says, patients may benefit most from a combination of therapies that target both the cancer cells and parts of the microenvironment that support their growth.
Learn more: Turning cells against pancreatic cancer
The Latest on: Pancreatic cancer
via Google News
The Latest on: Pancreatic cancer
- ‘The 10 Percent Club’: Researchers Try To Determine Why Some Pancreatic Cancer Patients Outlive The Oddson October 17, 2019 at 3:34 pm
PITTSBURGH (KDKA) – Six years ago, Kathy Miller had severe pain in her back. She thought it was her gallbladder. She was stunned when the doctors told her it was pancreatic cancer. “It just kind of ...
- 'The 10 Percent Club': Local Woman With Pancreatic Cancer Defies The Oddson October 17, 2019 at 3:27 pm
Researchers are trying to figure out how some pancreatic cancer patients outlive the odds; KDKA's Dr. Maria Simbra reports. 'The 10 Percent Club': Local Woman With Pancreatic Cancer Defies The ...
- How Alex Trebek Is Fighting Back Against Pancreatic Canceron October 17, 2019 at 10:00 am
host has been educating his followers on something infinitely more important and far more personal. "Just like 50,000 other people in the United States each year, this week I was diagnosed with stage ...
- Lilly's Pancreatic Cancer Candidate Fails in Phase III Studyon October 17, 2019 at 9:12 am
Eli Lilly and Company LLY announced that its immunotherapy candidate, pegilodecakin, in combination with chemotherapies, failed to show survival benefit in a phase III SEQUOIA study, evaluating the ...
- SPOP suppresses pancreatic cancer progression by promoting the degradation of NANOGon October 17, 2019 at 8:26 am
It appears to help regulate progression of several cancers, and we show here that it acts as a tumor suppressor in pancreatic cancer. Our analysis of patient tissues showed decreased SPOP expression, ...
- Eli Lilly's experimental pancreatic cancer drug fails in phase 3 trialon October 17, 2019 at 8:09 am
INDIANAPOLIS — An experimental cancer drug by Eli Lilly has failed in its phase 3 study with metastatic pancreatic cancer, the company announced this week. Indianapolis-based Eli Lilly said Wednesday ...
- PhRMA takes on Pelosi & a costly pancreatic cancer failureon October 17, 2019 at 7:38 am
Pelosi’s drug pricing plan puts medical innovation at risk Pelosi’s drug pricing plan puts medical innovation at risk Here’s a brain teaser: Surprising study shows reduced neuronal… Here’s a brain ...
- “Bills Dad” raising money to find cure for pancreatic canceron October 17, 2019 at 7:25 am
BUFFALO, N.Y. (WIVB) — We all know him as the “Bills Dad,” but his real name is Dick DeGroat, and he’s trying to raise money to find a cure for pancreatic cancer. DeGroat is known for posting videos ...
- Lilly experimental drug fails in late-stage trial for pancreatic canceron October 16, 2019 at 8:59 am
Shares of Eli Lilly and Co. dipped Wednesday morning after the Indianapolis-based drugmaker said its highly touted experimental pancreatic cancer treatment failed to meet its goal of overall survival ...
via Bing News