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Progress Report: Andrea Harzstark, MD

Investigator: Andrea Harzstark, MD – Assistant Professor, University of California, San Francisco

Tobacco and Prostate Cancer Therapy: The Missing Link?

Prostate cancer affects one in every six American men; ~25% of those men are smokers. Smoking causes many health risks, including a higher risk for lung cancer. Many of the chemicals found in tobacco can cause mutations (genetic alterations that can confer cancer). Moreover, nicotine, the most abundant chemical in cigarettes, has been shown to directly increase the growth and survival of endothelial cells (cells that form blood vessels) by elevating the levels of a protein called Vascular Endothelial Growth Factor (VEGF). In patients with any type of cancer this is problematic because tumor survival is largely dependent upon the supply of blood. Tumors grow their own network of blood vessels through a process known as angiogenesis. Induction of angiogenesis is largely driven by increased levels of VEGF.

Dr. Andrea Harzstark is interested in assessing whether exposure to nicotine from smoking may impair therapy response in men with prostate cancer. She is conducting two independent studies. The first is a retrospective study; she will analyze the data collected from a clinical trial of prostate cancer patients who were treated with an agent called Bevacizumab, which blocks VEGF. From this trial she will determine whether a patient was a smoker by testing stored urine or blood for levels of a smoking-specific protein called cotinine. She will also assess the levels of VEGF found in the blood or urine of the same patient specimens. Dr. Harzstark can then use the compiled clinical data to assess whether smokers have increased levels of VEGF and whether this increase was associated with a better or worse clinical outcome. The results will identify whether patients who smoke benefit from treatment with agents like Bevacizumab which block VEGF.

Dr. Harzstark’s second study is a prospective clinical investigation in which she will investigate the impact of smoking on drug metabolism (how the body breaks down a drug to unleash its function). Since smoking causes the ingestion of numerous chemicals, these chemicals may enhance or block the effect of therapies. The study will determine whether prostate cancer patients who smoke respond to docetaxel therapy (first-line chemotherapy for advanced prostate cancer) better or worse than non-smokers. Taken together, these studies will define whether non-smokers and smokers respond to therapies differently and may indicate that smokers and non-smokers must be treated distinctly. For example, in lung cancer treatment, patients who are smokers receive a different treatment regimen than patients who are non-smokers because of their differences in response to therapies.