||5R21CA218732-02 Interpret this number
||University Of Tx Md Anderson Can Ctr
||PANCFIT: Do Angiogenic Biomarkers Correlate with Improved Progression Free Survival in Pancreatic Cancer?
Pancreatic adenocarcinoma patients have a 5-year overall survival rate of less than 10%, unless these patients can undergo
curative surgery. Patients who will undergo surgery first receive chemotherapy treatment to improve the likelihood of
success of the surgery. However, the vast majority of patients are not surgical candidates due to disease dissemination,
and are therefore treated with only a combination of multiple chemotherapies. For these patients as well as those who are
candidates for surgery, improved chemotherapy efficacy would likely significantly improve survival rates. One way to
improve chemotherapy efficacy is to increase delivery of chemotherapy specifically to the tumor by improving tumor
vascular function. We have demonstrated in mouse models of pancreatic cancer that moderate aerobic exercise causes
tumor vasculature to remodel and become more functional, leading to better chemotherapy delivery to the tumor and
ultimately better anti-tumor efficacy. We also demonstrated that tumor vascular normalization in response to exercise is
dependent on increased Thrombospondin-1 (TSP-1) in the serum. Importantly, our pilot study in human patients with
pancreatic cancer patients demonstrated that a home-based aerobic and resistance exercise program is safe and feasible
during the time after diagnosis, during chemotherapy, chemoradiation, and rest, prior to surgery. Here, we propose to
evaluate tumor vascular remodeling and serum levels of TSP-1 to determine whether these are biomarkers of response to
exercise, which we hypothesize will correlate with improved chemotherapy efficacy and thus better patient outcome.
Patient outcome will include physical fitness and strength, as well as the percent of surgical candidates who are able to
undergo surgery. We will evaluate blood and surgical tumor specimens, as well as patient outcomes, from patients in a
randomized clinical trial comparing standard of care (recommendation to exercise) to a home-based, structured exercise
program consisting of 150 minutes per week of walking and resistance exercise during the time that patients are actively
receiving chemotherapy, chemoraidation, or are recovering prior to surgery.
Exercise during preoperative therapy increases tumor vascularity in pancreatic tumor patients.
Florez Bedoya C.A.
, Cardoso A.C.F.
, Parker N.
, Ngo-Huang A.
, Petzel M.Q.
, Kim M.P.
, Fogelman D.
, Romero S.G.
, Wang H.
, Park M.
, et al.
Scientific reports, 2019-09-27; 9(1), p. 13966.