'Achilles heel' of pancreatic cancer identified

May 1, 2014, Georgetown University Medical Center

A research team at Georgetown Lombardi Comprehensive Cancer Center reports that inhibiting a single protein completely shuts down growth of pancreatic cancer, a highly lethal disease with no effective therapy.

Their study, published online today in Science Signaling, demonstrates in animal models and in human cancer cells that while suppressing Yes-associated protein (Yap) did not prevent pancreatic cancer from first developing, it stopped any further growth.

"We believe this is the true Achilles heel of pancreatic cancer, because knocking out Yap crushes this really aggressive cancer. This appears to be the critical switch that promotes cancer growth and progression," says the study's senior investigator, Chunling Yi, PhD, an assistant professor of oncology at Georgetown Lombardi.

Yi added that because Yap is over-expressed in other cancers, such as lung, liver and stomach tumors, researchers are already working on small molecule drugs that will inhibit activity of the protein and its partnering molecules.

The study was conducted in mouse models of (PDAC), which accounts for all but five percent of human pancreatic cancers. These mice have a mutation in the KRAS gene, as well as a mutation in their p53 gene. "More than 95 percent of pancreatic cancer patients have a KRAS mutation and about 75 percent have a mutation in p53, so these mice provide a natural model of the human disease," she says.

Because it has been very difficult to devise drugs that target either KRAS or p53, in this study the researchers looked for other potential druggable targets involved in uncontrolled growth of pancreatic cancer.

They found that Yap was over-expressed in both mouse models and human samples of PDAC, and they discovered that the KRAS mutation found in most pancreatic cancer activates Yap. "The KRAS mutation uses Yap to make grow, so shutting down Yap defuses the mutated gene's activity," Yi says.

Yap also shuts down activity of the p53 oncogene, though the link between p53 and Yap is not yet known.

"KRAS and are two of the most mutated genes in human cancers, so our hope is that a drug that inhibits Yap will work in patients—who have both —and in other cancers with one or both mutations," Yi says.

Explore further: New drug combinations may benefit patients with pancreatic cancer

Related Stories

New drug combinations may benefit patients with pancreatic cancer

October 21, 2013
Two drug combinations that simultaneously block two major signaling pathways downstream of the protein KRAS, which is aberrantly active in most pancreatic cancers, may provide a new treatment option for patients with this ...

EGFR essential for the development of pancreatic cancer

September 15, 2011
The epidermal growth factor receptor (EGFR) gene is essential for KRAS-driven pancreatic cancer development, according to study results presented at the Second AACR International Conference on Frontiers in Basic Cancer Research, ...

Gene linked to pancreatic cancer growth, study finds

January 31, 2012
A mutant protein found in nearly all pancreatic cancers plays a role not only in the cancer's development but in its continued growth, according to a new study from University of Michigan Comprehensive Cancer Center researchers. ...

Cancer-causing gene alone doesn't trigger pancreatic cancer, study finds

September 10, 2012
More than a cancer-causing gene is needed to trigger pancreatic cancer, a study led by Mayo Clinic has found. A second factor creates a "perfect storm" that allows tumors to form, the researchers say. The study, published ...

Gene discovery links cancer cell 'recycling' system to potential new therapy

May 1, 2014
University of Rochester scientists have discovered a gene with a critical link to pancreatic cancer, and further investigation in mice shows that by blocking the gene's most important function, researchers can slow the disease ...

Recommended for you

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

Presurgical targeted therapy delays relapse of high-risk stage 3 melanoma

January 17, 2018
A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at ...

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.