Exercise during preoperative therapy increases tumor vascularity in pancreatic tumor patients

Abstract

The efficacy of chemotherapy is reduced by dysfunctional tumor vasculature, which may limit chemotherapy delivery to tumors. Preclinical studies have shown that moderate aerobic exercise improves tumor vascular function and increases chemotherapy efficacy in mouse models, but the effect of exercise on human tumor vasculature has not yet been determined. Here, we demonstrate that exercise remodels the tumor vasculature, accelerates the regression, and delays the regrowth of pancreatic ductal adenocarcinoma in a patient-derived xenograft mouse model treated with gemcitabine. By evaluating pancreatic adenocarcinoma specimens from patients treated with preoperative chemotherapy or chemoradiation therapy, we also demonstrate for the first time that tumor vascular remodeling occurs in association with exercise in humans. Future studies will evaluate whether exercise-induced vascular remodeling improves gemcitabine or other chemotherapy efficacy in patients, as this study evaluated only changes in tumor vascular structure.

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

“…In one detailed study on a mouse xenograft model of PDAC, the combination of gemcitabine plus treadmill walking inhibited tumor growth significantly more than gemcitabine alone [336]. The same effect was seen in a PDX model of PDAC (Figure 18A) [38]. The latter study also showed that the time taken for tumors to regress was significantly (ca.…”

“…Therefore, one possible method for improving outcomes for patients receiving standard chemotherapy is to improve the vasculature within the tumor. In addition, exercise can reduce fatigue, fitness loss, as well as improve mental health and the psychosocial downside of treatment [38].…”

“…The benefits of combining treatment with exercise were confirmed in a pilot study on PDAC patients (Table 1, U). Thus, 70 patients with potentially resectable PDAC were prescribed an exercise regime concurrently with preoperative chemotherapy and/or chemoradiation [38]. Of the 70 patients enrolled, 33 (47%) underwent resection of their primary tumor.…”

“…In conclusion, animal models and human studies agree in showing that exercise can enhance the effectiveness of clinical treatment of PDAC. As regards, how much exercise would be optimal, in the study of Bedoya et al [38], this involved at least 120 min of moderate-intensity, home-based exercise (60 min of aerobic exercise and 60 min of 'strengthening' per week). The "prehab" group had exercised for a mean of ca.…”

Feasibility and Acceptability Findings of an Energy Balance Data Repository of Children, Adolescents, and Young Adults with Cancer

“…Specifically, in children and AYA with cancer, malnutrition—including both over and undernutrition—is a risk factor for inferior cancer-related outcomes [ 4 ] and PA is associated with improved quality of life and physical function [ 5 ]. There are also emerging preclinical data that suggest that PA may improve tumor response to treatment [ 6 , 7 ] and that obesity may reduce tumor response to treatment via adipocyte signaling [ 8 ]. Both the intake and expenditure aspects of the EB equation as they relate to cancer outcomes will be reviewed briefly below.…”