Associate Professor of Medicine
Steven Stratton, PhD is Associate Professor of Medicine in the University of Arizona Cancer Center, and is a previous recipient of a K07 Career Development Award from the NIH. He is trained in analytical chemistry, molecular toxicology, cancer pharmacology, clinical research, and drug development. Current research areas include skin cancer chemoprevention drug development, prostate cancer prevention, and biomarker development. He has performed several large, randomized clinical trials in cancer and cancer prevention serving as Principal Investigator or Co-Principal Investigator, four of which involved drugs partially developed by him involving his investigator-initiated submissions of Investigational New Drug (IND) applications to the FDA. He is also currently the Clinical Project Leader and Co-Director of the Drug Development Core for the Chemoprevention of Skin Cancer Program Project and Co-Director of the Prostate Cancer Prevention Program. His research is currently funded by the National Cancer Institute as well as several research contracts and clinical trial agreements with biotech and pharmaceutical companies. His administrative roles include Co-Director of the Analytical Chemistry Shared Resource and Chairman of the Medical Research Committee in the College of Medicine at the University of Arizona. In these roles, he is responsible for oversight of scientific, logistic, and regulatory aspects of clinical research.
Skin Cancer Research
Skin cancer is the most common malignancy in the world. One out of three new cancers is an invasive skin cancer. The overall goal of Dr. Stratton's research in skin cancer is to develop new therapeutic strategies to eradicate skin pre-cancers, and identify high-risk groups who can benefit from these strategies. In a collaborative team science environment, he conducts a multilevel program of rational drug development for skin cancer, including: 1) the identification of critical molecular targets in solar radiation-induced signaling pathways in skin; 2) the selection of chemopreventive drugs that specifically “hit” these molecular targets and definitively interrupt their signaling pathways; 3) testing of the most promising target-specific agents in preclinical pharmacology and toxicology models required for Investigational New Drug (IND) applications; and 4) conducting early-stage clinical trials to prove target validity and drug tolerability/efficacy.
So far ~10 clinical trials have been performed or are ongoing with hundreds of participants. The average retention rate for thesestudies is >90%, a testament to the extensive experience and expertise of the clinical staff. In one of the first signaling studies, published in Photochemistry and Photobiology the skin biomarker group, led by Dr. Janine Einspahr, analyzed whether: solar-simulated light (SSL) mediates activation of the p38 MAP kinase and PI-3 kinase-Akt signaling pathways resulting in c-Fos and COX-2 expression in human skin. Participants agreed to receive a dose of SSL administered to non-sun exposed skin. The dose was equivalent to one that would produce a mild sunburn, and biopsies were taken at various times following SSL exposure. Protein expression patterns in these biopsies were in agreement with mouse studies in many cases, which means that the mouse models have some validity in predicting a human skin response. These data suggest that UV acts through p38 MAPK and PI-3 kinase with phosphorylation of MAPKAP2, CREB, c-JUN, p38, GSK-3β, and p53; leading to increases in expression of c-FOS, COX-2, and apoptosis.
Another, larger, clinical trial analyzed the effect of daily topical perillyl alcohol (a component of the lavender plant and the skin of cherries) on sun-damaged skin in 75 people. This Investigator-initiated Phase 2a, Randomized, Placebo-controlled, Double-blind Trial was published in Cancer Prevention Research. No effect on sun damage was observed clinically, but nuclear morphometric analysis indicated a potential protective effect. Current efforts are focused on two new trials, opening in December, 2014. The first trial led by Dr. Clara Curiel is using Reverse-Phase Protein Array technology to analyze the effect of solar-simulated light on the skin of patients who are just about to begin cancer therapy with select targeted kinase inhibitors such as vemurafenib and sorafenib. Results could be used to predict those patients who will have adverse effects to these drugs, and may provide a model to help select personalized therapies in cancer patients. The second trial, led by Dr. Stratton, will analyze the effects of a common topical emollient on morphology and protein expression in solar keratosis, a precursor to skin cancer. Both studies will utilize Reflectance Confocal Microscopy, using the expertise of Dr. Curiel to visualize changes in skin non-invasively.
Prostate Cancer Research
Dr. Stratton's research interests in prostate cancer include clinical exploration of secondary prevention strategies as well as biomarker development for diagnosis and prognosis. The effect of selenium on prostate cancer prevention has been widely studied and debated for almost two decades. The large Phase 3 SELECT trial definitively showed that selenomethionine was not effective in prostate cancer prevention in healthy men. However, the effect of selenized yeast was still debated, as this was the form of selenium used in the original studies that predicated the idea of selenium in prostate cancer prevention. The prostate group led by Dr. Stratton recently published the results of a Phase 3 trial of selenized yeast (daily up to 5 years) in men who had a negative biopsy for prostate cancer (a high-risk group). This Phase 3 randomized, double-blind, placebo-controlled clinical study (the Negative Biopsy Trial) was conducted in 699 men with PSA >4 ng/ml and/or a suspicious digital rectal examination. Participants were randomized to receive daily oral placebo, 200 mg selenium, or 400 mg selenium as selenized yeast. They were followed every 6 months for up to 5 years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox proportional hazards model.. Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 mg/day or the selenium 400 mg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7], respectively. This study showed that daily selenized yeast had no effect on future development of prostate cancer in these men, compared to placebo. This work, published in The Prostate, appears to close the book on selenium and prostate cancer prevention. However, this and other studies left a treasure trove of blood and tissue samples from these men that are being used to explore other aspects of prostate cancer. For example, the: prostate biopsy is the gold standard test for diagnosing prostate cancer, but it is associated with a rather large sampling error.
In collaboration with Drs. Anne Cress and Ray Nagle, Dr. Amit Algotar in Dr. Stratton's laboratory used markers associated with DNA damage and repair to attempt to improve the diagnostic accuracy of prostate biopsies in men at high risk for PCa. Biopsy samples from men participating in the Negative Biopsy Trial (73 subjects and 146 matched controls) were stained immunohistochemically for pRAD51 and gamma H2AX. Image analysis using ScanScope and Spectrum software from Aperio Technologies showed that subjects diagnosed with PCa demonstrated higher expressions of both gamma H2AX (mean(SD), 33.8(17.7) and 19.4(14.5)) as well as pRAD51 (55.8(24.1) and (44.7(26.5)). As compared to a statistical model containing baseline PSA, age and race, the model containing pRAD51 and gamma H2AX combined showed improved positive predictive value, improved negative predictive value and increased AUC (70%, 78.9%, 0.77 and 80%, 87.06%, 0.90 respectively, p= 0.025). Thus, markers associated with DNA damage and repair may be developed to improve the diagnostic accuracy of a prostate biopsy for cancer.
Bermudez, Y., Stratton, S.P., Curiel-Lewandrowski, C., Warneke, J., Hu, C., Bowden, G.T., Dickinson, S., Dong, Z., Bode, A., Saboda, K., Brooks, C.A., Petricoin, E.F. III, Hurst, C.A., Alberts, D.S., and Einspahr, J.G. Activation of the PI3K/Akt/mTOR and MAP kinase signaling pathways in response to acute solar simulated light exposure of human skin (submitted) 2014.
Williams, J.D., Bermudez, Y., Park, S.L., Stratton, S.P., Uchida, K., Hurst, C.A., Wondrak, G.T. Malondialdehyde- derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue. J Photochem Photobiol B. 132: 56-65, 2014.
Algotar, A.M., Behnejad, R., Stratton, M.S., and Stratton, S.P. Chronic use of NSAIDs and/or statins does not affect PSA or PSA velocity in men at high risk for prostate cancer. Cancer Epidemiol Biomarkers Prev 23:2196-2198, 2014.
Algotar, A.M., Hsu, C.H., Singh, P., and Stratton, S.P. Selenium supplementation has no effect on serum glucose levels in men at high risk for prostate cancer. J Diabetes 5:465-470, 2013.
Algotar, A.M., Stratton, M.S., Ahmann, F.R., Ranger-Moore, J., Nagle, R.B., Thompson, P.A., Slate, E., Hsu, C.H., Dalkin, B.L., Sindhwani, P., Holmes, M.A., Tuckey, J.A., Graham, D.L., Parnes, H.L., Clark, L.C., and Stratton, S.P. Phase 3 clinical trial investigating the effect of selenium supplementation in men at high risk for prostate cancer. Prostate 73:328-335, 2013.
Einspahr, J.G., Calvert, V., Alberts, D.S., Curiel-Lewandrowski, C., Warneke, J., Krouse, R., Stratton, S.P., Liotta, L., Longo, C., Pellicani, G., Prasad, A., Sagerman, P., Bermudez, Y., Deng, J., Bowden, G.T., Petricoin, E.F. 3rd. Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. Cancer Prev Res. 5:403-413, 2012.
Algotar, A.M., Thompson, P.A., Ranger-Moore, J., Stratton, M.S., Hsu, C.H., Ahmann, F.R., Nagle, R.B., and Stratton, S.P. Differences in characteristics of men with localized prostate cancer who demonstrate low, intermediate or high PSA velocity. Intern Med J 42:374-380, 2012.
Algotar, A.M., Stratton, S.P., Ranger-Moore, J., Stratton, M.S., Hsu, C.H., Ahmann, F.R., and Thompson, P.A. Obesity and smoking as risk factors for prostate cancer progression. Am J Men’s Health 5:272-278, 2011.
Algotar, A.M., Stratton, M.S., Xu, M.J., Dalkin, B.L., Nagle, R.B., Hsu, C.H., Ahmann, F.R., Clark, L.C., and Stratton, S.P. Effect of selenium supplementation on selenium levels within the prostate. Nutr Cancer 63:1-5, 2011.
Algotar, A.M., Stratton, M.S., Stratton, S.P., Hsu, C.H., and Ahmann, F.R. No effect of selenium supplementation on blood glucose levels in men with prostate cancer. Am J Med 123:765-768, 2010.
Algotar, A.M., Thompson, P.A., Ranger-Moore, J., Stratton, M.S., Hsu, C.H., Ahmann, F.R., Nagle, R.B., and Stratton, S.P. Effect of aspirin, other NSAIDs and statins on PSA and PSA velocity. Prostate 70:883-888, 2010.
Stratton, M.S., Algotar, A.M., Ranger-Moore, J., Stratton, S.P., Slate, E., Hsu, C.H., Thompson, P.A., Clark, L.C., and Ahmann, F.R. Oral selenium supplementation has no effect on PSA velocity in men undergoing active surveillance for localized prostate cancer. Cancer Prev Res 3:1035-1043, 2010.
Stratton, S.P., Alberts, D.S., Einspahr, J.G., Sagerman, P.M., Warneke, J.A., Curiel-Lewandrowski, C., Myrdal, P.B., Karlage, K.L., Nickoloff, B.J., Brooks, C., Saboda, K., Yozwiak, M.L., Krutzsch, M.F., Hu, C., Lluria-Prevatt, M., Dong, Z., Bowden, G.T., and Bartels, P.H. A Phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer. Cancer Prev Res 3:160-169, 2010.
Skin Cancer Research Collaborators
David Alberts, MD
Clara Curiel, MD
Sally Dickinson, PhD
Zigang Dong, DrPH (University of Minnesota)
Janine Einspahr, PhD
Emanuel Petricoin, PhD (George Mason University)
Prostate Cancer Research Collaborators
M. Suzanne Stratton, PhD
Amit Algotar, MBBS, PhD
Frederick Ahmann, MD
Ray Nagle, MD, PhD
Anne Cress, PhD
Parminder Singh, MD
Cancer affects us all, and everyone has a loved one touched by cancer. This is a common motivation. The biology of cancer, and it's relationship to life itself (e.g. cancer is driven by a cell's confusion about whether to live or die), is fascinating and makes this disease truly the 'mother of all maladies'. The opportunity to make a difference in improving public health as it relates to cancer is what prompted me to get into cancer research.
American Association for Cancer Research (AACR)
American Society of Clinical Oncology (ASCO)
Society of Toxicology (SOT)
American Association for the Advancement of Science (AAAS)
Association of Clinical Research Professionals (ACRP)
- Sydney E. Salmon, MD, Distinguished Junior Investigator Award, 2012
- First Decade Award, Gustavus Adolphus College, 2000
- National Cancer Institute Post-Doctoral Training Grant Fellow, 1998-2000
- University of Arizona Graduate College Registration Scholarship, 1994-1995
- National Institute of Environmental Health Sciences Pre-Doctoral Training Grant Fellow, 1991-1994
- Honorable Mention, Society of Toxicology Tenth Annual Graduate Student Awards for Meritorious Research in Mechanisms of Toxicology, 1992
- Student Travel Award, Society of Toxicology Annual Meeting, Seattle, WA, 1992
- Graduate College Fellowship, University of Arizona, 1990
- American Institute of Chemists Achievement Award for Senior Student Majoring in Chemistry, Gustavus Adolphus College, 1990
- F.E. Knock Scholarship for Chemistry Students, Gustavus Adolphus College, 1990
- Partners in Scholarship Award for Outstanding Academic Achievement, Gustavus Adolphus College, 1986-1990
- Lutheran Brotherhood Member Scholarship, Gustavus Adolphus College, 1986-1990
- Albert Steinke Memorial Scholarship for Post-Secondary Education, Gustavus Adolphus College, 1986-1990