Collaboration Produces New Proteomic Technology to Aid in Cancer Research

Posted: May 23, 2005 at 1:00 am, Last Updated: November 30, -0001 at 12:00 am

By Patty Snellings

Using a new type of proteomic technology, scientists at George Mason and the National Cancer Institute (NCI) have identified a hyperactive network of cancer cell proteins that may lead to a strategy to boost the survival rate for children suffering from rhabdomyosarcoma, a highly aggressive form of childhood cancer. Rhabdomyosarcoma is the cause of more than 50 percent of soft-tissue cancers in children and accounts for 5-8 percent of all childhood cancers.

Lance Liotta and Emanuel Petricoin III, codirectors of the university’s Center for Applied Proteomics and Molecular Medicine, along with Lee Helman, chief of pediatric oncology at NCI, recently presented their findings at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Fla.

More than 3,800 abstracts were submitted to ASCO this year to announce breaking news and innovative advances in cancer research and clinical applications to an audience of approximately 28,000 of the world’s leading oncology professionals. The rhabdomyosarcoma abstract also was selected through a peer-review process as one of 42 papers for inclusion in the Best of ASCO educational programs, which will be presented at various locations in the United States and abroad later in the year, including the Best of ASCO meeting in Japan.

“This study is an excellent example of how proteomics can generate new strategies for more effective disease treatment and optimized patient care,” Liotta says.

Proteomics, the study of protein activity in cells, is an emerging field in medicine that holds the promise of a new paradigm for early disease detection and personalized medical treatment.

The preliminary study, using protein microarray technology developed by Liotta and Petricoin, identified three interconnecting proteins in rhabdomyosarcoma tumors that segregate patient response to conventional chemotherapy, which is ineffective in 30-40 percent of children with the disease.

Proteins can link together and form pathways inside a cell. Pathways inside a cancer cell often become hyperactive and encourage the cell to grow and invade other cells. When the pathway containing the three proteins identified in the rhabdomyosarcoma study is suppressed, treatment is successful and prognosis is good. However, treatment response is poor when the protein pathway is active.

“This is the first time that proteomic technologies have been used to predict which patients will respond to therapy and why,” explains Petricoin. “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.”

Ongoing research will further validate these findings, according to the scientists.

“Many human diseases, such as diabetes, obesity, and cardiovascular conditions also are underpinned by deranged pathways,” Liotta adds, “so we think the development of this new type of proteomic technology will help uncover new drug targets, or pathways that respond to treatment, for critical areas other than cancer.”

A discussion of the protein microarray technology used in this study was published in the May 20, 2005, issue of the Journal of Clinical Oncology, along with case studies from Laser Capture Microdissected human breast and colorectal carcinomas that support the feasibility of applying these technologies to clinical research.

A technology widely used in laboratories throughout the United States and invented several years ago by Liotta and colleagues at NCI, Laser Capture Microdissection is a process used to rapidly pluck diseased cells directly from a biopsy sample. Diseased cells in the sample are surrounded by other tissue activity, and this process segregates the cells of the evolving disease for analysis and leaves behind unnecessary cellular information.

Reverse phase protein microarray technology takes thousands of cells and produces a detailed quantitative analysis on more than a hundred signaling proteins, both activated and suppressed, at once. An analysis of the resulting diagram indicates whether the various protein pathways are linked together and activated or suppressed, and helps scientists understand more about the protein activity associated with a particular disease.

“These are examples of innovative proteomic technologies currently in use that will assist in determining treatment and follow-up care for patients with diseases. For the first time,” says Petricoin, “we can profile the ongoing state of protein pathways in a biopsy specimen. We are hopeful that this new information may ultimately lead to patient-tailored treatment and new clinical trial designs, and effect a positive impact on public health.”

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