Introduction: Naturally occurring compounds play an essential role in the prevention and treatment of various cancers. There are more than 100 plant and animal based natural compoundscurrently in clinical use. Areas covered: 1) The importance of natural products combinations in the prevention and treatment of cancer, 2) the need to maximize efficacy while minimizing side effects when using natural product combinations, and 3) specifics related to plant and animal derived natural products, as well as agents derived from natural products. Therapies using natural compounds that have been investigated, their rationale, mechanism of action and findings are reviewed. When the data warrant it, combined interventions that appear to increase efficacy (compared with monotherapy) while minimizing toxicity have been highlighted. Pubmed was used to search for relevant publications. Expert opinion: Combination therapy with natural compounds has the potential to be more effective than single-agent therapy. Similar to pharmacologic agents, the goal is to maximize efficacy while mimimizing potential side effects. There is an increasing research focus on the development of agents derived from natural products, with notable successes already achieved from the effort.

To evade immune surveillance, tumors develop a hostile microenvironment that inhibits anti-tumor immunity. Recent immunotherapy breakthroughs that target the reinvigoration of tumor-infiltrating T lymphocytes (TIL) have led to unprecedented success in treating some cancers that are resistant to conventional therapy, suggesting that T cells play a pivotal role in anti-tumor immunity. In the hostile tumor microenvironment (TME), activated T cells are known to mainly rely on aerobic glycolysis to facilitate their proliferation and anti-tumor function. However, TILs usually exhibit an exhausted phenotype and impaired anti-tumor activity due to the limited availability of key nutrients (e.g., glucose) in the TME. Given that different T cell subsets have unique metabolic pathways which determine their effector function, this review introduces our current understanding of T cell development, activation signals and metabolic pathways. Moreover, emerging evidence suggests that fatty acid binding protein 5 (FABP5) expression in T cells regulates T cell lipid metabolism and function. We highlight how FABP5 regulates fatty acid uptake and oxidation, thus shaping the survival and function of different T cell subsets in the TME.

Metabolic syndrome consists of a constellation of clinical factors associated with an increased risk of cardiovascular disease, type 2 diabetes, and cancer. Preclinical studies demonstrate that restricting the time during a 24-hour period when an obese animal eats (time-restricted feeding) leads to metabolic benefits. These benefits, which may or may not be associated with weight loss, often lead to improvements in glucose tolerance and insulin sensitivity. Studies seeking to determine whether similar benefits result when humans restrict daily eating time (time-restricted eating) are less mature and less consistent in their findings. In this commentary, we outline some of the exciting preclinical findings, the challenges that preliminary studies in humans present, and efforts of the US National Institutes of Health and specifically the National Cancer Institute to address the role of time-restricted eating in cancer.

Multiple agents derived from natural products (NPs) have been evaluated for cancer prevention and interception, either alone or in combination. The National Cancer Institute (NCI) is very interested in advancing research to identify additional agents that, alone or in combination, may prove useful in cancer prevention. Below, we provide an overview of NP studies in cancer prevention and interception, both individual agents and combination interventions. Given that findings from many preclinical studies evaluating individual agents have generally not been confirmed in human studies, our focus with individual NPs in this review is on studies involving humans, especially clinical trials. Fewer combination intervention studies have been conducted, so we have broadened our review to include preclinical studies. We conclude with how the Division of Cancer Prevention (DCP) within the NCI is providing funding to encourage the research community to propose natural product studies in cancer prevention and interception to advance the field.