Table 5.

Recommendations for Preclinical Exercise Oncology Research

Concern	Recommendation
Use of xenograft models in immune deficit animals	Orthotopic implantation of syngeneic tumor cell lines or induction of orthotopic tumors via transgenic or chemical methods in immune competent animals
Poor description of exercise intervention characteristics	Describe frequency, intensity, duration, and progression, as appropriate. Avoid vague terms such as “exercise to exhaustion”. Confirmation of ‘training’ effect via muscle fiber or mitochondrial function analysis
Handling of control (sedentary) animals	Handling, social interaction, and environment should be similar to animals randomized to exercise conditions. This includes differences in cage size and social housing. If possible, animals should be acclimated to exercise, or introduced to the activity gradually.
Tail vein models of metastasis	Consider using orthotopic implantation of syngeneic tumor cell lines or transgenic models that spontaneously develop metastasis. However, tail vein models of metastasis may still be useful for assessing the effects of exercise at later time points in the metastatic cascade.
Lack of assessment of systemic and molecular mechanisms	Investigate effects on systemic mechanisms (metabolic and sex hormones, inflammation, immunity, and products of oxidation) postulated to underlie effects of exercise on tumorigenesis as well as potential mediating molecular mechanisms (e.g., cell signaling pathways, angiogenesis, metabolism, migration). Findings should be validated by the use of knock-out/knock-in transgenic animals.
Lack of assessment of tumor biology beyond tumor incidence, weight, or volume	Report on other common markers of the neoplastic phenotype (e.g., apoptosis, proliferation, microvessel density, necrosis, angiogenesis)
Lack of concern regarding the psychological differences between voluntary physical activity vs. forced exercise	Comprehensive study on hypothalamic- pituitary- adrenal axis activation in response to different exercise prescriptions and the effects that associated hormones have on tumor progression/prevention in sedentary controls.