Proteomics Research Offers Promise for Cancer Treatment

Posted: September 19, 2005 at 1:00 am, Last Updated: November 30, -0001 at 12:00 am

Lance Liotta and colleague Virginia Espina use laser capture microdissection to segregate diseased cells from other cellular material in a tissue biopsy.

By Patty Snellings

When a Federal Express delivery arrives at the Prince William Campus, it’s not always your typical package. It might include a tissue biopsy extracted from a man undergoing treatment for lung cancer at M.D. Anderson Cancer Center in Houston, Texas, or a blood specimen drawn from a patient suspected of having ovarian cancer at Memorial Sloan-Kettering Cancer Center in New York City.

Doctors at these and other premier medical institutions are turning to George Mason’s Center for Applied Proteomics and Molecular Medicine for explanations to complex medical puzzles so they can better evaluate and treat their patients’ illnesses.

An estimated 570,280 deaths from cancer will occur this year, while 1,372,910 new cases will be diagnosed. One in four deaths is caused by cancer, and 1,500 people die from the disease each day. These staggering statistics from the American Cancer Society point to cancer as the second leading cause of death (behind heart disease) in the United States.

A New Paradigm for Personalized Medicine

The Center for Applied Proteomics and Molecular Medicine, part of the Life Sciences initiative in the College of Arts and Sciences, is directed by Lance Liotta, formerly of the National Cancer Institute, and Emanuel Petricoin III, who came to the university from the U.S. Food and Drug Administration.

Proteomics—the study of protein activity in cells—is an emerging field in biomedical research. It holds the promise of a future where the individuality of a patient’s disease state determines tailored therapies and personalized management.

Petrocoin and Liotta
Virginia Espina, Emanuel Petricoin and Lance Liotta have a discussion in their Prince William Campus lab.
Photos by Evan Cantwell

“Patient-tailored medicine is the future of clinical practice, and we feel that George Mason is in a unique position to be a leader in this new era,” says Liotta.

To accelerate the work of the center, George Mason and Inova Health System have created a unique partnership to move cutting-edge discoveries and technologies directly to patient management and care through clinical trials and patient-tailored research at the bedside.

“George Mason’s vision to accelerate the impact that proteomics can have on patient care is so exciting to us,” Petricoin says. “The expanding investment into applied research and its unique and powerful relationship with Inova are the catalysts for realizing this promise.”

Proteomics Research at George Mason

An estimated 400,000 to 10,000,000 different proteins (the proteome) perform cellular functions in the 20,000 to 25,000 genes that construct the human genome. In contrast to the static nature of the genome, the dynamic proteome — the working machinery of the cell — is constantly changing in response to tens of thousands of signals from inside and outside the cellular environment.

The pioneering research led by Liotta and Petricoin focuses on the analysis of molecular pathways in diseased tissue to determine individualized and targeted treatment for patients; and on the discovery and identification of proteins in the blood that may be markers for early disease detection, prognosis and treatment.

They have developed proteomic technologies that can identify diseased pathways, which help predict which patients will respond to treatment and why.

“But proteomics can go beyond a prediction and help us understand which pathways to pursue in patients who, based on that prediction, are destined to fail conventional therapies,” says Petricoin.

The team recently discovered an archive of protein fragments in the blood that may be disease markers for ovarian cancer. The fragments have been identified, measured and analyzed, including a specific fragment of BRCA2, a gene associated with an inherited risk for ovarian and breast cancer. The findings will be published in the October issue of Clinical Chemistry and currently appear online in the journal.

“Although we have suspected the existence of these fragments in the past, this is the first study where we have actually identified and named the molecules,” Liotta says. “This gives us an untapped source of proteins from diverse tissue and cellular origin that may offer vital disease-related information.”

Tools for a Healthier Tomorrow

Liotta and Petricoin have developed and implemented numerous groundbreaking scientific principles and proteomic technologies since they began their collaborative research in 1997:

  • Mass spectrometry, a technology that can rapidly sort molecules based on size and other properties, generates potentially diagnostic proteomic fingerprints that identify and quantify disease-specific proteins.
  • The team recently discovered molecular “mops” that harvest disease markers in the blood. These “mops” are naturally occurring bloodborne molecules that bind to disease-related markers previously unknown to exist. This discovery may profoundly impact research aimed at markers for early disease detection.
  • Reverse phase protein microarray technology takes thousands of cells from a tiny biopsy specimen and produces a detailed quantitative analysis of the cellular circuitry. Using this technology, Liotta and Petricoin have identified a hyperactive pathway that is a new target for therapy and can predict patient response to chemotherapy for rhabdomyosarcoma, a highly aggressive form of childhood cancer.
  • Laser capture microdissection, invented several years ago by Liotta and colleagues at NCI, is a commercialized technology that is widely used in laboratories throughout the United States. Using a laser beam to rapidly pluck microscopic diseased cells directly from a biopsy sample, this process segregates the cells of the evolving disease for analysis and leaves behind unnecessary cellular information.

Liotta explains that many human diseases, such as diabetes, obesity and cardiovascular conditions, also are underpinned by deranged pathways.

“We think the development of new proteomic technologies will help uncover new drug targets, or pathways that respond to treatment, for critical areas other than cancer,” he says.

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