Nutrigenomics and cancer therapy.

As an increasingly prevalent disease and a leading cause of death, cancer is a major threat to human health. Although cancer research has provided us with a better understanding of cancer biology, we still face numerous challenges in cancer treatment and prevention. Current therapies are largely limited to surgery, radiation therapy, and chemotherapy, which remain unsatisfactory. In particular, there are many problems in chemotherapy, such as low response rate, poor specificity, drug resistance, and severe side effects. Thus, we still have much to do in order to improve the current situation. It is our priority to identify and develop alternative treatment options that can increase efficacy, reduce side effects, and improve quality of life for cancer patients. In this context, nutrigenomics is emerging as a field that holds great promise for this endeavor because of its capability to modulate cancer metabolism and tumorigenesis through nutritional intervention. Cancer metabolism has gained unprecedented attention due to its involvement in every stage of cancer development. Cancer cells are characterized by an altered metabolism to sustain their rapid growth. One well-recognized alteration is the reprogramming of cellular energy production, known as the Warburg effect: unlike normal cells that primarily utilize oxidative phosphorylation, cancer cells predominantly produce energy by a high rate of glycolysis followed by lactic acid fermentation, and thus require a large supply of glucose [1] . Recent studies have revealed that changes in gene expression, such as phosphofructokinase 1 [2] and pyruvate kinase type M2 [3] , are implicated in this altered pathway. Cancer cells also exhibit an increased production of certain metabolites that serve as building blocks to meet proliferation requirements. In particular, lipid synthesis is enhanced in cancer cells by the upregulation of fatty acid-metabolizing enzymes, such as fatty acid synthase [4] , stearoyl-CoA desaturase-1 [5] , and delta-6 desaturase [6] . Furthermore, the production of factors that support the tumor microenvironment is augmented in cancer cells. For example, one well-known metabolic biomarker of cancer is the overexpression of cyclooxygenase-2, which is responsible for converting omega-6 arachidonic acid into tumor-promoting eicosanoids [7] . It is clear that nutrient metabolism is critical for cancer biology, and thus modulation of the metabolic pathways would have profound effects on cancer development. Certain nutrients have been shown to be capable of modulating gene expression related to cancer hallmarks, such as inflammation, angiogenesis, and proliferation, through multiple mechanisms. For example, polyunsaturated fatty acids (PUFA) can influence gene expression