Epidemiological studies
A greater number of large-scale studies assessing both self-reported and/or objective measures of exercise exposure with long-term follow-up and adequate event rates. Delineate the association no how changes in exercise behavior, functional capacity/cardiorespiratory fitness measures are associated with clinical outcome across all solid tumors. More studies determining the differential association between exercise and prognosis as a function of tumor phenotype/gene expression. More studies determining the differential association between exercise and prognosis as a function of host-related circulating factors postulated to mediate the exercise–prognosis relationship.
|
Clinical biomarker intervention studies
Delineate the differential effects of differences in exercise prescription dose (e.g., frequency, intensity, duration, modality) on changes in salient biomarkers in randomized trials. Determine effects of exercise across different tumor types across the cancer continuum (i.e., from diagnosis to palliation) to expand current efforts as well as extend to other solid tumors where exercise has not been rigorously evaluated. Elucidate the most salient biomarkers of interest that mediate the exercise–cancer prognosis relationship to develop a standardized ‘exercise–oncology’ biomarker panel that is reproducible and can be evaluated/compared across studies. Determine the effects of exercise on circulating biomarkers in conjunction with procurement of tumor tissue and/or imaging biomarkers whenever possible.
|
Preclinical studies
Orthotopic implantation of syngeneic tumor cell lines or induction of orthotopic tumors via transgenic or chemical methods in immune competent animals to enable investigation of effects on primary tumor growth and metastasis. Elucidate the optimal exercise frequency, intensity, duration, and progression, as appropriate. Confirmation of ‘training’ effect via muscle fiber or mitochondrial function analysis. Determine effects on systemic mechanisms (metabolic and sex hormones, inflammation, immunity, and products of oxidation) in conjunction with examination of intratumoral/tumor microenvironmental molecular mechanisms (e.g., cell signaling pathways, angiogenesis, metabolism, migration).
|
Potential translational (cross-cutting/transdisciplinary) studies
Elucidation of the optimal dose of exercise to inhibit tumor progression/metastasis in mouse models of solid tumors to guide the dose of exercise to be tested in phase II randomized trials. Elucidation of the effects of exercise on both circulating and intratumoral mechanisms associated with tumor growth in mouse models to guide systemic (plasma) biomarker testing in completed and ongoing clinical exercise trials in cancer patients. For further mechanistic investigations, plasma/serum from patients exposed to exercise vs. control conditions can be applied to human cancer cells in vitro to investigate effects on markers of the neoplastic phenotype. In epidemiological studies, identify genes or histological sub-types that may mediate the association between exercise and prognosis. Next, in preclinical studies, confirm mechanism of action by examining the effects of exercise in clinically relevant mouse models where the identified gene/pathway/histological sub-type is over-expressed or ablated. For clinical translational, plasma/serum from patients (with the identified histological sub-type or over expression of a specific pathway) exposed to exercise vs. control conditions can be applied to human cancer cells in vitro for further mechanistic studies.
|
