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News

Case research team heading to home base with Pc 4

Case Western Reserve University : 26 January, 2007  (Technical Article)
A professional baseball player at the plate hits the ball one out three times at bat. For a chemist in the drug development business, the odds of making a new drug are much longer, one in 5,000. Even as a long shot, the work of Malcolm Kenney, a Case Western Reserve University professor of chemistry, and Nancy Oleinick, a Case professor of radiation oncology, shows promise of scoring with the development of Pc 4, a photosensitizer for photodynamic therapy of cancer.
Along with Kenney and Oleinick, a team of researchers from the Case School of Medicine and University Hospitals of Cleveland are making strides with Pc 4. Currently in a Phase 1 clinical trial, Pc 4 shows early signs of being able to beat a variety of cancers, including its newest use in fighting skin cancers.

Since 1956, Kenney has designed and synthesized thousands of the bright-blue phthalocyanine compounds. Pc 4 is among them.

In the early 1980s, Oleinick began assembling a team from radiology and dermatology departments of Case and from the Ireland Cancer Center of University Hospitals to investigate the potential use of PDT as an alternative treatment for cancer patients, who exhausted their tolerance for radiation therapy.

In looking across campus, Oleinick discovered that Kenney had 30 years of experience in designing and synthesizing phthalocyanines, and that some of the compounds which he had made were potential PDT compounds.

Shortly after learning of Kenney’s work, Oleinick invited Kenney to become the research group’s primary chemist and to have as his mission the development of new PDT drugs. Kenney began by selecting 20 of his compounds. Oleinick then studied how well they worked.

With information from the original 20 compounds, Kenney and his research team returned to the chemistry lab and synthesized six new compounds (Pc 1- Pc 6). Again Oleinick again studied the new compounds. Of those compounds, Pc 4 consistently performed better on cancer cell cultures and in mice with tumors in the lab setting, said Oleinick. Shortly after those studies, the research team developed a project that won funding by the National Cancer Institute.

PDT is not a new science. The ancient Egyptians rubbed plants containing natural photosensitizers on diseased areas of their skin. In sunlight, the treated areas sometimes responded favorably.

During the 1970s, the first generation of modern PDT drugs was developed. Building on this work, the Case scientists searched for a second-generation photosensitizing drug through Kenney’s research.

PDT works through the use of the red portion of visible light. The red portion penetrates tissue well and is able to energize a photosensitive drug and cause it to burn away cancer cells. Because it absorbs red light, Pc 4 is a brilliant blue.

In patients with internal cancers such as breast cancer or head-and-neck cancer who are being treated with the first-generation photosensitizer or with Pc 4, the drug is injected intravenously and reaches cancer cells in tumors. After 24 to 48 hours, the patient, kept away from bright lights to prevent activation of the photosensitizers which have found their way into the skin, undergoes a laser treatment targeted to the cancerous area of the body. Following the treatment with the first-generation photosensitizer, the patient needs to remain in low-level lights for several weeks to prevent excessive burning from the photosensitiver remaining in the skin. Skin photosensitivity is lower with Pc 4.

In a new clinical trial for skin cancer, Pc 4 is applied directly to skin lesions. After approximately one hour during which the patient is under normal light, a laser physicist directs the high-powered laser on the lesion to kill the cancer cells. This new simple procedure is being directed by Elma Baron, assistant professor of dermatology, and Kevin Cooper, professor and chair of dermatology.

“It’s normal for a new drug to take a long time to reach clinical trials,” said Kenney.

The group received FDA approval for its first clinical trials in 2001 through the Ireland Cancer Center at the University Hospitals under the direction of Timothy Kinsella, professor and chair of radiation oncology. Clinical trials have continued; patients who meet the qualifications for participation are needed.

Kenney said that Pc 4, which comes out of a train of research in his laboratories on phthalocyanines extending over almost 50 years, could be rounding the bases to be that one chemical hit in 5,000. But he said, as in baseball, “the game isn’t over ‘til it’s over.”
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