The following description was taken from the R01 version of this FOA.
The goal of this Funding Opportunity Announcement (FOA) is to stimulate transdisciplinary and translational research that will identify the specific biological or biobehavioral pathways through which physical activity and/or weight control (either weight loss or avoidance of weight gain) may affect cancer prognosis and survival. Studies of the effects of diet modification or caloric restriction alone on biomarkers are not be appropriate for this FOA. Research applications should test the effects of physical activity, alone or in combination with weight control (either weight loss or avoidance of weight gain), on biomarkers of cancer prognosis among cancer survivors identified by previous animal or observational research on established biomarkers other than insulin/glucose metabolism, especially those obtained from tumor tissue sourced from repeat biopsies where available. Biomarkers may include but are not limited to intervention-induced changes in sex hormones, insulin-like growth factors or their binding proteins, leptin and other adipokines, immunologic or inflammatory factors, oxidative stress and DNA damage or repair capacity, angiogenesis, or prostaglandins. Many cancer survivor populations will not experience recurrence but will die of comorbid diseases (e.g., cardiovascular disease) or may experience early effects of aging. Accordingly, inclusion of biomarkers of comorbid diseases (e.g., markers of chronic inflammation, bone turnover markers for osteoporosis/fall risk) and of the aging process (e.g., telomere length, p16INK4a) are also sought.
This FOA is suitable for projects where proof-of-principle of the proposed technology or methodology has already been established and supportive preliminary data are available.
This FOA runs in parallel with an FOA of identical scientific scope, PAR-18-892, which utilizes the Exploratory/Developmental Grant (R21) mechanism.
Cancer Survivorship, Obesity, and Physical Activity: There are over 15.5 million cancer survivors in the United States and this number will increase dramatically with the aging of the US population. Whether cured or living with cancer as a chronic condition, survivors suffer higher rates of morbidity and mortality than their unaffected peers. There is a pressing need to identify interventions for survivors that may improve long-term prognosis and survival. Two potential interventions may be physical activity and weight control. Population-based National Health Interview Survey data indicate that 47-65% of survivors are overweight or obese. This problem is compounded by the increasing trend toward obesity in the general population, the increased risk for cancer conferred by excess body weight, and the weight gain common after certain cancer treatments. The prevalence of overweight and obesity is high among childhood cancer survivors as well; these survivors are twice as likely to be obese compared to their siblings, particularly among females. Further, 68-80% of adult survivors do not meet national physical activity guidelines, depending on cancer site. Despite discussion in the literature that cancer is a teachable moment for health promotion, cancer survivors are not much more likely to be physically active compared to their healthy peers.
Biological Mechanisms of Lifestyle Interventions: Recent systematic reviews and meta-analyses of results using cohort study data document that excess body weight increases risk for recurrence and second cancers and decreases overall survival. These results also suggest that physical activity decreases the risk of mortality among cancer survivors, and the effect may be independent of weight loss. However, the biobehavioral mechanisms and pathways through which lifestyle interventions may increase survival following cancer are unknown. Prior research suggests that excess body weight or physical inactivity may increase risk of poor prognosis and survival through effects on sex hormones, insulin or insulin-like growth factors or their binding proteins, insulin resistance, glucose metabolism, leptin and other adipokines, immunologic or inflammatory factors, oxidative stress and DNA damage or repair capacity, angiogenesis, or prostaglandins. However, these potential mechanisms and pathways have been identified primarily from animal models and observational studies. Randomized clinical trials (RCTs) or other experimental design approaches testing the effects of weight control and/or physical activity on these pathways would delineate how these lifestyle interventions may influence prognosis and survival in humans. Finally, understanding the pathways through which these interventions are effective would help identify the optimal type and intensity of intervention(s) and determine who is most likely to benefit from these interventions by cancer type, age, or other host factors. This information extends and leverages the knowledge that could be gained from a survival trial or epidemiological study, and identifies biomarkers for monitoring of the success of behavioral interventions, which also may increase intervention adherence when provided as feedback to participants.
Applications submitted to this FOA should test the effects of physical activity or weight control or both interventions on biomarkers of cancer prognosis among cancer survivors. Applications may use experimental research designs (e.g., RCTs, fractional factorial designs…etc.) or non-experimental designs. Applications should bring together transdisciplinary teams of investigators with expertise in behavioral intervention, cancer biology, and other basic and clinical science disciplines relevant to the pathways being studied.
Applications with animal model aims are particularly encouraged, but each application needs to include at least one aim that conducts, or analyzes data from, a physical activity or weight control intervention in human cancer survivors.
Research topics of interest include but are not limited to:
A) Clinical studies to determine the optimal type and intensity of intervention for different subgroups of cancer survivors (e.g., by age, cancer type, or other host factors), especially in comparison to generalized health promotion recommendations:
- Does the magnitude of the effect of weight control and/or physical activity on cancer prognostic biomarkers differ by mode of exercise (i.e., resistance training vs. aerobic training)? Does the effect of weight loss on cancer prognostic biomarkers differ for overweight/obese cancer survivors with different cancer subtypes (e.g., triple-negative compared to ER+ breast cancer, specific genetic subtypes of colon cancer, or varying severity of Gleason score for prostate cancer)?
- What is the effect of two different intensities of aerobic physical activity intervention over 6 months on endocrine parameters in childhood cancer survivors under age 18? How are the effects of physical activity on cancer prognostic biomarkers different in older adult vs. younger adult cancer survivors or among those with multiple comorbidities?
- Do gene variants and/or epigenetic factors interact with physical activity and weight loss to influence biomarkers of survival (are there subgroups that benefit relatively more or less from these behaviors)?
- How can we better understand the effects of physical activity or weight control interventions in survivors who are “metabolically obese” but not phenotypically obese (their underlying biology reflects the effects of obesity without excess weight), or in those who are obese but have high levels of cardiorespiratory fitness?
B) Studies with animal model components:
- How can animal models of human cancers be used to expose the genetic and environmental underpinnings of the effects of physical activity and/or weight control on the biology of tumors?
- How can animal models be used to devise and test intervention approaches that are suitable for human studies, and to develop imaging and other biomarkers that indicate efficacy of interventions?
- How can information learned from animal models be used to refine the testing of interventions in human cancer survivors?
- Do physical activity and/or weight control early in life alter epigenetic mechanisms that influence cancer survival later in life (or in subsequent generations)?
The following types of projects are not appropriate for this FOA:
- Studies of the effects of diet modification or caloric restriction alone on biomarkers will not be appropriate for this FOA, since the goal is to stimulate new science and not repeat existing studies testing the effects of diet on cancer biomarkers.
- Additionally, while cachexia and malnourishment in cancer survivors are important factors for prognosis and survival, the mechanisms underlying these effects are likely different and outside the scope of this FOA.
Deadlines: standard dates and standard AIDS dates apply
- R01 – https://grants.nih.gov/grants/guide/pa-files/PAR-18-893.html
- R21 – https://grants.nih.gov/grants/guide/pa-files/PAR-18-892.html
Filed Under: Funding Opportunities