Findings on chemoprevention provide hope

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Association: The Prostate Health Index, a blood test used to evaluate the probability of prostate cancer diagnosis, outperformed two commonly used tests—the prostate-specific antigen and free/total prostatespecific antigen—in predicting the presence of clinically significant prostate cancer and in improving prostate cancer detection, according to a new study by Emory urology chair Martin Sanda, who presented the finding at the association’s May meeting.

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A new research finding from Winship is proof-of-principle that precancerous oral lesions can be prevented from transforming into squamous cell carcinoma. Dong Shin (pictured below), professor of hematology, oncology, and otolaryngology and director of Winship’s Cancer Chemoprevention program, published the findings in Clinical Cancer Research. The next step for investigation is exploring whether the same results can be duplicated by using nontoxic chemicals, such as those found in green tea and red wine. The original study used agents that do have toxicity.

Based on prior research suggesting a role for epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in promoting squamous cell carcinoma of the head and neck (SCCHN), Shin and colleagues hypothesized that combining an EGFR inhibitor and a COX-2 inhibitor could provide an effective chemopreventive approach.

They found that the combination of the EGFR inhibitor erlotinib and the COX-2 inhibitor celecoxib was more effective for inhibiting the growth of human SCCHN cell lines compared with either drug alone. In addition, treating mice with the drug combination prior to transplanting them with human SCCHN cells more effectively suppressed cancer cell growth than did pretreating the mice with either drug alone.

Based on these preclinical findings, Shin and colleagues initiated a phase I chemoprevention trial. Eleven patients with advanced oral precancerous lesions were assigned to treatment with erlotinib and celecoxib. Tissue samples from the patients were obtained and evaluated pathologically at three, six, and 12 months after therapy initiation. Biopsies at baseline and follow-up were available for seven patients.

“Prevention is not achieved through short-term treatment,” Shin says. “So, we are investigating the safety and toxicity of this combination further before planning a large-scale trial. We also are looking to combination therapies using less toxic compounds.”

That combo would include Polyphenon-E, one of the active ingredients in green tea, which Shin has spent years studying in the laboratory.

“It would be great if we could treat these lesions with less toxic chemicals, such as those found in green tea, and still achieve the same effect,” Shin says.