Exercise training in cancer survivors has beneficial effects to mitigate disease- and treatment-related side effects, improves quality of life and reduces the risk for recurrence and cancer and non-cancer mortality. However, there are numerous hurdles to dissemination of exercise training to the broader cancer population. Central among these is that patients may be unable or unwilling to participate in facility-based, exercise training programs, the traditional model for delivery of exercise to clinical populations. Thus, there is a clear need to develop alternative exercise modalities that are effective at producing an exercise stimulus, require minimal costs and equipment and integrate easily into the outpatient and home environment. To address this need, our long-term goal is to develop clinically useful exercise interventions that can serve as alternatives to facility-based exercise programs, with the objectives of alleviating fatigue, forestalling disability and improving prognosis. Our objective in this R21 application is to determine whether exercise training via neuromuscular electrical stimulation (NMES) has beneficial effects on skeletal muscle size and function in cancer patients. NMES permits extracorporeal initiation of muscle contractions that can mimic resistance- or aerobic-type exercise. Because it produces these effects with little effort from the patient, is inexpensive, simple to use and is portable to the outpatient clinic and home environments, NMES represents a promising candidate exercise modality for cancer survivors unable to participate in facility-based programs because of availability of facilities or clinical limitations. Our overall hypothesis is that NMES will improve skeletal muscle size, contractile function and oxidative capacity. We will use data from cancer patients studied prior to and 8 wks following completion of NMES or control intervention to determine the effects of NMES on these three fundamental skeletal muscle characteristics assessed at the cellular and organellar levels. The rationale for performing these assessments is built on our seminal work describing deficits in skeletal muscle at these anatomic levels that contribute to physical disability in cancer survivors and our preliminary data showing that NMES counteracts these deficits. In this context, we aim to provide proof-of-principle evidence for the utility of NMES to improve cellular- and organellar-level deficits that contribute to fatigue and disability in cancer patients. Successful completion of the proposed studies will impact the oncology rehabilitation field by providing a solid, mechanistic evidence base to support larger-scale, randomized, and controlled trials of the efficacy of NMES in cancer survivors. More broadly, NMES holds the potential to extend the benefits of exercise to the broader cancer survivor population that will be underserved by facility-based exercise training programs.