Basic Translational Science
The CIRCL is investigating the molecular mechanisms by which cholesterol, carbohydrates, caloric restriction, exercise and obesity regulate tumor growth. In a recent study published in Cancer Research, we describe a novel cholesterol-signaling axis (CYP27A1-27HC) that is frequently lost in prostate cancer and that, when restored, inhibits prostate cancer cell growth in vitro and in vivo. In addition, we recently conducted a functional genomic screen in obese and calorie-restricted mice to identify drug-able targets that drive prostate cancer growth in obese hosts or that can be targeted in combination with caloric restriction (diet) to slow tumor growth even further. Lastly, complementing our Carbohydrate and Prostate Cancer (CAPS2) clinical trial, we are continuing to investigate the effects of low carbohydrate diets in pre-clinical mouse models and are also testing the effects of carbohydrate quality (high glycemic index vs. low glycemic index) on tumor growth.
Currently, Richard Waldron, PhD, is leading the study, Revealing Mediators of Obesity-Promoted Pancreatic Adenocarcinoma, to elucidate mechanisms whereby a high fat, high calorie Western diet promotes advancement of pancreatic cancer. Pancreas from mice expressing oncogenic mutant KRas and raised on different diets will be subjected to state-of-the-art quantitative proteomic analysis at Cedars-Sinai to determine key proteins either increased or decreased in both males and females over time. This information will enable reconstruction of the signaling and metabolic pathways, and may identify novel biomarkers that emerge at distinct stages of the disease progression.
The epidemiologic research of the CIRCL focuses on lifestyle factors that may influence cancer racial disparities in minority populations. Recent projects have aimed at understanding how inflammation caused by dietary carcinogens may in part be responsible for the disproportionally higher prostate and cervical cancer incidence and mortality rates in the African American population. Additionally, we focus on finding correlations between diet, lifestyle and cancer risk. For example, studies have shown that obese men are more likely to have aggressive prostate cancer, including progression after surgery.
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