Within the Cedars-Sinai Center for Integrated Research in Cancer and Lifestyle (CIRCL), our basic science team focuses on identifying the molecular mechanisms by which lifestyle factors and dietary interventions influence cancer growth, with the hope of developing better disease-management and therapeutic strategies.
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.
Current clinical trials examine how diet, exercise, or both contribute to cancer recurrence and overall survival. Epidemiological data point to weight-loss, low carbohydrate diets and high-intensity exercise as factors that affect cancer. However, only a randomized controlled clinical trial can study whether these factors play a role in improved cancer outcomes. Cedars-Sinai is currently conducting four randomized clinical trials in different cancer types and stages (prostate, breast and ovarian cancer) to further examine these hypotheses.
Optimal cancer care requires an understanding of a treatment's impact on an individual's clinical condition, functional capacity and quality of life. However, real-time assessments of how functional or symptomatic a patient has been outside the four walls of the clinic can be challenging for a number of reasons. In the study, Exploratory Study Evaluating the Longitudinal Integration of Wearable Biosensors into Cancer Clinical Trials to Assess Physical Functioning and Distress in Patients with Advanced Cancer, the research team will be evaluating the feasibility of utilizing wearable biosensors (e.g., Fitbits) in therapeutic clinical trials for patients with advanced cancer as an objective, real-time and dynamic assessment of a patient's physical functioning and a measure of experienced distress.
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