Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Novel method could help bring cancer biomarkers to clinic

An international team of scientists led by Fred Hutchinson Cancer Research Center cancer proteomics expert Amanda Paulovich, M.D., has demonstrated the feasibility of large-scale, standardized protein measurements, which are necessary for validation of disease biomarkers and drug targets.

The study, to be published Dec. 8 online in the journal Nature Methods, shows that the scientists' targeted protein-detection approach has the potential to systematically and reliably measure the entire human repertoire of proteins, known as the proteome.

The technique, developed by Paulovich, a member of Fred Hutch's Clinical Research Division, and her colleagues, can simultaneously and precisely detect the abundance of hundreds of proteins in many different samples. Researchers from three different groups in Seattle, Boston and South Korea were able to reproduce measurements of 319 proteins from human breast cancer cells, showing that the method can be standardized across laboratory and international boundaries.

"This method has the potential to completely revolutionize how we measure human proteins," Paulovich said. "Having a global resource for standardized quantification of all human proteins would set new standards that would undoubtedly increase the reproducibility of preclinical research, which would have a dramatic impact on the translation of novel therapeutics and diagnostics."

Proteins, the molecular workhorses of all biological functions, hold the key to signaling early disease and disease progression. Cancer biomarkers are especially sought after – the protein fingerprints in cells could lead to tests to detect the disease earlier, to identify a person's specific risk of cancer long before it develops, and to better guide patients' treatments. But validating newly discovered biomarker candidates has proven impossible without standardized and reproducible methods to measure their levels, Paulovich said.

Each promising biomarker must be further studied in clinical trials, which requires researchers to measure the abundance of each candidate biomarker in hundreds to thousands of patient samples. Because the odds are extraordinarily low that any one candidate will translate to clinical use, large numbers of proteins must be tested to identify a clinically useful biomarker.

"Right now, you can't make robust measurements of most human proteins," Paulovich said. "More than 10 years after the human genome has been sequenced and we have the full catalog of molecules as important as proteins, we still can't study the human proteome with any kind of throughput in a standardized, quantitative manner."

To address this problem, Paulovich and her colleagues used a sensitive and targeted protein-measurement technology called multiple reaction monitoring mass spectrometry, or MRM-MS. This type of mass spectrometry is not new – it has been used for years in clinical laboratories worldwide to measure drug metabolites and small molecules associated with inborn errors of metabolism. More recently, Paulovich and others have begun using it to measure human proteins.

The researchers' method enables highly specific, precise, multiplex (meaning the technique measures several different proteins in a single experimental assay) quantification of a minimum of 170 proteins in 20 clinical samples per instrument per day; no other existing technology has this power.

Because the mass spectrometry technique is targeted, meaning the researchers can tune the instruments to look for a specific subset of proteins in cancer cells or other sample types, it can detect the presence of proteins of interest at much lower levels in tiny blood samples or biopsies than a non-targeted tactic.

"The goal is to position this technology to displace some very old technologies that are currently being used," said Jacob Kennedy, an analytical chemist in Paulovich's group and lead author of the study.

Currently, researchers usually use either Western blotting, ELISA (enzyme-linked immunosorbent assay), or immunohistochemistry (IHC) techniques to measure levels of proteins in clinical samples. These methods are often not reproducible from laboratory to laboratory, rendering validation of candidate biomarkers for clinical use very difficult, and they cannot be used for large numbers of proteins and samples at once.

Paulovich and her colleagues assayed more than 300 proteins known to be produced by breast cancer cells to validate their technique; their results showed that MRM-MS could recapitulate and extend observations made in previous studies of breast cancer using other technologies.

The study, which included collaborating research groups from the Broad Institute in Cambridge, Mass., and the Seoul National University and Korea Institute of Science and Technology, South Korea, demonstrated MRM-MS's capacity to measure many proteins at once in a standardized way, laying the foundation for an international, organized effort to quantitate every protein in the human proteome. Their study – the largest to demonstrate the technique's reproducibility across laboratories and the only international study to do so – has pushed the capacity of the technology the farthest, measuring hundreds of protein pieces where others have measured dozens.

"We really showed what could happen if governments cooperated to build a community resource," she said. "It's doable, it's scalable, and the resource is useful."

Paulovich's team hopes the technique catches on in research communities around the world. To facilitate this, her group is spearheading the development of an open-source website to create a centralized resource of highly validated assays for the research community. The portal, funded by the Clinical Proteomics Tumor Analysis Consortium Initiative (CPTAC) of the National Cancer Institute, is set to launch in early 2014.

The National Institutes of Health, the National Cancer Institute, the Breast Cancer Relief Foundation, The Foster Foundation and the National Research Foundation of Korea funded the research.

Note for media: To obtain a copy of the Nature Methods paper, "Demonstrating the feasibility of large-scale development of standardized assays to quantify human proteins," please contact the journal at

At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch's pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer with minimal side effects. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation's first and largest cancer prevention research program, as well as the clinical coordinating center of the Women's Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs. For more information visit or follow Fred Hutch on Facebook, Twitter or YouTube.


Deborah Bach

Deborah Bach | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Molecular doorstop could be key to new tuberculosis drugs
20.03.2018 | Rockefeller University

nachricht Modified biomaterials self-assemble on temperature cues
20.03.2018 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Physicists made crystal lattice from polaritons

20.03.2018 | Physics and Astronomy

Mars' oceans formed early, possibly aided by massive volcanic eruptions

20.03.2018 | Physics and Astronomy

Thawing permafrost produces more methane than expected

20.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>