The high rate of recurrent disease is a critical barrier to promote the health and longevity of colon cancer (CC) survivors. An approach to reduce this barrier is to develop interventions to minimize recurrence that CC survivors can accomplish autonomously, such as lifestyle and behavioral modification. Observational epidemiologic data suggest physical activity after diagnosis of CC reduces the risk of cancer recurrence by 40%, CC-specific mortality by 45-71%, and all-cause mortality by 57-63%. However, the underlying biological pathway of this association remains uncharacterized. Excess visceral adipose tissue (VAT) and hyperinsulinemia play a pivotal role in the development of recurrent and metastatic disease among CC survivors. VAT is an independent predictor of disease-free survival, CC-specific mortality, and all-cause mortality among CC survivors. VAT is metabolically active and lends rise to the development of hyperinsulinemia. Insulin stimulates the growth and proliferation of CC cells, acting as a catalyst to promote the initiation and progression of recurrent and metastatic disease. Reducing VAT and insulin may favorably alter the risk of developing recurrent and metastatic disease, and improve the quality and longevity of CC survivorship. Aerobic exercise reduces VAT and insulin in dose-response fashion among non-diabetic persons with obesity. However, the dose-response effects of exercise on VAT and insulin have not been characterized specifically among CC survivors. To address this knowledge gap, we will leverage the commencement of a phase II, randomized, six-month, dose-response exercise trial (The COURAGE Trial; R21 CA182767) that will compare 150 min?wk-1 or 300 min?wk-1 of moderate-intensity aerobic exercise to a wait-list control group among 39 CC survivors. We will harness this trial by adding an innovative and recently-validated dual energy x-ray absorptiometry-based methodology to quantify VAT, and use existing blood samples to quantify fasting insulin. The primary aims of this trial are to quantify and describe the dose response effects of moderate-intensity aerobic exercise on VAT and fasting insulin. We will explore the correlation between improvements in VAT and improvements in fasting insulin. Equipping the COURAGE trial with these measurements provides a unique opportunity to glean complementary knowledge about the dose-response effects of exercise on biomarkers, such as VAT and insulin, which are implicated in CC outcomes. This research experience is coupled with a set of didactic courses with cross-cutting themes that include cancer epidemiology, nursing science, and cancer biology.
The aims of this research are consistent with NCI provocative question PQA-2, which seeks to elucidate how varying doses of exercise influence cancer prognosis and prognostic biomarkers.
Exercise has emerged as a potential lifestyle intervention to reduce cancer recurrence and improve survival among people with colon cancer. The biological pathway through which exercise reduces cancer recurrence and improves survival is unclear. This study will leverage an ongoing clinical trial to identify the dose-response effects of exercis on biomarkers associated with colon cancer prognosis.
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