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Nowhere to Hide | Dennis Hallahan, John Gore, peptide, light-emitting tag, Vanderbilt Ingram Cancer Center, Vanderbilt University Institute of Imaging Science, Vanderbilt In Vivo Cellular and Molecular Imaging Center, ICMIC, cell death, cancer

Vanderbilt Researchers Illuminate Cancer Treatments that Truly Work

Every minute counts when a patient is battling cancer. The last thing a physician wants to do is waste time on a treatment regimen that isn't optimal.

Thanks to groundbreaking research at Vanderbilt, oncologists may soon know in days... rather than weeks or months... if tumors are responding to a prescribed protocol.

The good news, said Dennis E. Hallahan, MD, chair of Radiation Oncology at Vanderbilt University Medical Center, is that numerous treatment options exist these days for most every type of cancer. "Molecular targeted therapies shrink cancers but don't affect other tissues. They bind to molecules in cancer and interrupt the signaling … which ultimately causes slowing of the growth of the tumor or cell death within cancer."

The bad news, he continued, is that only a small percentage of patients respond to each of these highly personalized options "so their physician needs to determine which drug is appropriate for each person."

Currently, imaging techniques such as CT or MRI are used to measure a tumor's size after a course of treatment to see if there has been a response.

Unfortunately, Hallahan pointed out, "If the tumor continues to grow while on an ineffective therapy, that patient would essentially lose two or three months on ineffective therapy."

To narrow the data lag, Hallahan is leading a team of researchers in a quest to "light up" tumors as they die. In mouse models, cellular changes in response to treatment have been evident in as little as a single day.

NCI Grant Enhances Imaging Program

At the end of last year, Vanderbilt-Ingram Cancer Center and the Vanderbilt University Institute of Imaging Science received a sizeable grant to launch a new program. The $7.5 million cash infusion from the National Cancer Institute (NCI) will support the establishment of the Vanderbilt In Vivo Cellular and Molecular Imaging Center (ICMIC).

Dennis E. Hallahan, MD, co-principal investigator on the ICMIC project said the NCI has only made 10 such awards nationwide. The funding will allow Vanderbilt to develop innovative and significant molecular imaging studies such as his peptide project (see main story) to measure the response mechanism to targeted cancer treatments.

In addition to the research directed by Hallahan, the ICMIC grant will also initially fund imaging studies led by Robert Coffey, Jr., MD; Larry Marnett, PhD; and Lynn Matrisian, PhD.

Hallahan said funding would also be used to expand the scope of the core laboratories where new imaging tools are developed and to help train and develop the careers of young researchers.

When the funding was announced, John Gore, PhD, who is the principal investigator for the NCI grant and director of the Institute of Imaging Science, said, "This grant recognizes the success of our multidisciplinary approach to medical research and the results of our institutional investments in imaging in recent years."

Vanderbilt opened a state-of-the-art imaging center outfitted with the latest technology on Garland Avenue in November 2006.

"We developed a microscopic marker –– a tiny beacon –– that binds to dead and dying cells," he explained of the light-emitting tag attached to the peptides … small protein fragments analogous to a zip code or bar code … that are being used in the investigation. "Anytime you are developing an imaging agent, sensitivity and specificity are the two most important elements. Here, sensitivity is the ability of the peptide to detect all cancers that respond to treatment. Specificity is the ability of the peptide to discern between responding and non-responding cancers."

He continued, "As our armamentarium against cancer increases, we will have the ability to quickly assess the effectiveness of a drug and switch a patient if need be."

Over the eight years of research, Hallahan and his colleagues have now identified about two dozen peptides that cause dying human cancer cells in mouse models to glow in a manner that is easily visualized using PET or SPECT imaging. The handful of likely peptides was culled down from a library of more than a billion options.

Of the remaining group, Hallahan said it may turn out that one peptide will be more effective for signaling dying cells in brain cancer while another will be the optimal choice for colon cancer. The lead peptide, HVGGSSV, is now being developed for clinical trials and is in pre-clinical toxicity testing. Hallahan believes the pre-investigational new drug process, which typically takes a year to complete, will culminate in a presentation to the FDA by the end of 2009. Once approved by the federal agency, researchers typically expect to move to human clinical trials within 30 days.

While the surface benefits of such a marker are obvious for cancer patients and their oncologists, the technology actually has broader implications, as well. Not only will the marker guide physicians toward optimal treatment of a primary cancer, it could also signal the need for a mixed protocol in the case of metastatic cancer or a change in the regimen if the body develops a resistance to a therapy that was initially effective. Because monitoring is done through non-invasive imaging techniques, it could eliminate or greatly reduce the need for repeated biopsies, which are particularly difficult in cancers that are not easily accessed.

The discovery also holds great potential for the pharmaceutical industry.

"This imaging will help speed the development of new drugs brought into clinical trials by a pharmaceutical company," Hallahan noted, adding that the technology allows for better matching of drugs and patients in trials.

Hallahan said another plus of the peptide imaging agent is its ability to rapidly clear from the system. It's also easy and relatively inexpensive to produce and is expected to ultimately reduce the cost of healthcare by quickly shining a light on the most effective treatment measures.