Pancreatic ductal adenocarcinoma, or PDAC, is the fourth-leading cause of cancer-related death. Newly diagnosed patients have a median survival of less than one year, and a 5-year survival rate of only 3 to 5 percent. Therefore, biomarkers that can identify early onset of PDAC and which could be viable drug targets are desperately needed.
'"We found that a kinase called PEAK1 is turned on very early in pancreatic cancer," said first author Jonathan Kelber, PhD, a postdoctoral researcher in the UCSD Department of Pathology and Moores Cancer Center. "This protein was clearly detected in biopsies of malignant tumors from human patients – at the gene and the protein levels – as well as in mouse models."
PEAK1 is a type of tyrosine kinase – an enzyme, or type of protein, that speeds up chemical reactions and acts as an "on" or "off" switch in many cellular functions. The fact that PEAK1 expression is increased in human PDAC and that its catalytic activity is important for PDAC cell proliferation makes it an important candidate as a biomarker and therapeutic target for small molecule drug discovery.
In addition to showing that levels of PEAK1 are increased during PDAC progression, the scientists found that PEAK1 is necessary for the cancer to grow and metastasize.
"PEAK1 is a critical signaling hub, regulating cell migration and proliferation," said Kelber. "We found that if you knock it out in PDAC cells, they form significantly smaller tumors in preclinical mouse models and fail to metastasize efficiently."
The research team, led by principal investigator Richard Klemke, PhD, UCSD professor of pathology, studied a large, on-line data base of gene expression profiles to uncover the presence of PEAK1 in PDAC. These findings were corroborated at the protein level in patient biopsy samples from co-investigator Michael Bouvet, MD, and in mouse models developed by Andrew M. Lowy, MD, both of the UCSD Department of Surgery at Moores Cancer Center.
While many proteins are upregulated in cancers of the pancreas, there has been limited success in identifying candidates that, when inhibited, have potential as clinically approved therapeutics. However, the researchers found that inhibition of PEAK1-dependent signaling sensitized PDAC cells to existing chemotherapies such as Gemitabine, and immunotherapies such as Trastuzumab.
"Survival rates for patients with pancreatic cancer remain low," said Bouvet. "Therefore, earlier detection and novel treatment strategies are very important if we are going to make any progress against pancreatic cancer. Since current therapies are often ineffective, our hope is that the findings from this research will open up a new line of investigation to bring a PEAK1 inhibitor to the clinic."
Additional contributors to the study include Theresa Reno, Sharmeela Kaushal, Cristina Metildi,Tracy Wright, Konstantin Stoletov, Jessica M. Weems, Frederick D. Park, Evangeline Mose, UC San Diego; Yingchun Wang, Chinese Academy of Science, Beijing; and Robert M. Hoffman, UC San Diego and AntiCancer, Inc., San Diego.
The study was supported by the National Institutes of Health.
Debra Kain | EurekAlert!
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Earth Sciences
07.12.2016 | Earth Sciences
07.12.2016 | Materials Sciences