Translational and transdisciplinary research in energy balance and cancer: past is prologue

Obesity, defined as a body mass index ≥ 30 kg/m², is associated with an increased incidence of 13 cancers and increased mortality of 14 cancers (1,2). Obesity is strongly linked to poor diet and physical inactivity, which are also independent risk factors for cancer incidence and mortality (3-5). Estimates suggest that by 2030 obesity will overtake tobacco as the most common preventable risk factor for the development of cancer. Today, approximately 40% of US adults have a body mass index > 30 kg/m², with rates significantly higher in Black and Hispanic individuals, especially women (6). Rising rates of obesity and associated factors threaten to slow advances in cancer prevention and treatment, underscoring the critical need for research on the causal role of body composition, physical activity, and diet in cancer risk and outcomes.

Substantial gaps exist in our understanding of the relationship between energy balance and cancer. Much of the evidence to date has focused on breast cancer, generated from individuals of middle-to-higher socioeconomic status with early-stage malignancies (4). Research is needed to understand the role of obesity in influencing risk and outcomes of understudied obesity-associated cancers and in racial and ethnic minorities, patients undergoing active treatment or who have metastatic disease, cancer survivors with low income and who live in rural settings, as well as younger and geriatric populations. Mechanistic research is needed to elucidate associations of energy balance with the microbiome, epigenetics, immune function, immunotherapy, and cancer. Research is also needed on how to effectively implement and disseminate lifestyle interventions in oncology practice. In addition, research must focus on how to develop and assess successful multi-level intervention strategies at the individual and community levels. The National Cancer Institute Fiscal Year 2022 Annual Plan and Budget proposal featured obesity and cancer as a scientific topic and highlighted the importance of investing in training the next generation of cancer researchers (7). Transdisciplinary training is needed to prepare researchers to innovatively address these complex topics.

The National Cancer Institute–funded “Transdisciplinary Research in Energetics and Cancer (TREC) Training Program” is an annual 1-week, in-residence training course that includes mentoring and substantial networking. The program is geared toward early-career investigators from the basic, clinical, and population science disciplines (8). The goals of the TREC Training Program, funded from 2016 through 2026, are to educate, train, and mentor early-career investigators, called TREC Fellows, from basic, clinical, and population sciences in transdisciplinary research in energetics and cancer research. This training program was built on the National Cancer Institute U54 TREC-Centers Initiative, which was a major transdisciplinary scientific research effort that occurred from 2005 to 2016 (9). Investigators competitively accepted into the TREC Training Program collaborate with more than 20 expert TREC Faculty on developing grant proposals and/or manuscripts targeted toward key gaps in energy balance and cancer research. To date, 154 investigators from 92 institutions have completed the TREC Training Program. The overall impact of the TREC Training Program will be defined by the degree to which TREC Fellows produce innovative research approaches and discoveries, thereby accelerating the dissemination and implementation of evidence-based approaches into everyday practice and patient care and improving the health of the population at risk for cancer as well as those diagnosed with cancer.

This JNCI Monograph includes 15 manuscripts led or coauthored by TREC Fellows. As you will read in this issue, topics span the translational spectrum from pharmacokinetics of cancer therapeutics, ‘omics of skeletal muscle and obesity, body composition imaging modalities, sarcopenia, cachexia, bariatric surgery and pharmacotherapy approaches for cancer prevention, trends in diet and cancer research, intermittent fasting, metabolic and circadian rhythm and cancer outcomes, policy implications for exercise oncology, social and environmental factors affecting physical activity, and embedding lifestyle interventions into oncology care. Findings from these manuscripts provide more compelling evidence that to reach the Biden Moonshot goal to reduce the cancer mortality rate by at least 50% over the next 25 years (10), systems- and structural-level approaches will be needed to address rates of obesity and sedentary behavior and foster healthy lifestyles among cancer survivors and at-risk individuals. The Moonshot Initiative requires an “all-hands-on-deck approach involving the private sector, foundations, academic institutions, health care providers, and all Americans” (10) to reach the 50% cancer mortality reduction goal. It is imperative that future energy balance and oncology research and patient care take a similar approach, in particular systems- and structural-level transdisciplinary approaches, to end cancer as we know it.

Author contributions

Conceptualization: MLI, DS, JL. Methodology: MLI, DS, JL. Writing—original draft: MLI, DS, JL. Writing—review and editing: MLI, DS, JL. Funding acquisition: MLI.

Funding

This work was supported by the National Cancer Institute (R25CA203650) to MI.

Conflicts of interest

The authors declared no conflicts of interest.