Reduction of Chronic Hyperinsulinemia (Insulin Resistance) for the Prevention and Treatment of Cancerous Disease: The Crucial Role of Caloric Restriction

Gene’s expression changes with nutrition and physical activity and hormones signaling like insulin. A Western lifestyle may increase cancer risk through alterations in the metabolism of insulin and insulin-like growth factors. The anabolic signals by insulin or IGF-I can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. There is dynamic change in gene expression in response to nutritional availability [1]. A clear association between adiposity, physical inactivity and Western diet, and the risk of incident cancer, cancer recurrence and mortality after “curative” surgery is increasing. Insulin Resistance Status characterized by hyperinsulinemia is associated with an excessive increased risk for a number of malignancies. An increasing clinical, biological and epidemiological evidence sustain that Insulin-IGFs System has been implicated in breast, prostate, pediatric, colon-recto and gynecological cancers, including sarcomas, epithelial cancers, multiple myeloma and melanoma. Chronic hyperinsulinaemia may be a cause of cancers of the colon, pancreas, endometrium, breast, prostate, ovarium, and possibly of the lung, and may predispose strongly to melanoma development; reducing the hormone-vitamin D anticancerigen action [2].

Cytoskeletal Proteins in Cancer and Intracellular Stress: A Therapeutic Perspective

Cytoskeletal proteins, which consist of different sub-families of proteins including microtubules, actin and intermediate filaments, are essential for survival and cellular processes in both normal as well as cancer cells. However, in cancer cells, these mechanisms can be altered to promote tumour development and progression, whereby the functions of cytoskeletal proteins are co-opted to facilitate increased migrative and invasive capabilities, proliferation, as well as resistance to cellular and environmental stresses. Herein, we discuss the cytoskeletal responses to important intracellular stresses (such as mitochondrial, endoplasmic reticulum and oxidative stresses), and delineate the consequences of these responses, including effects on oncogenic signalling. In addition, we elaborate how the cytoskeleton and its associated molecules present themselves as therapeutic targets. The potential and limitations of targeting new classes of cytoskeletal proteins are also explored, in the context of developing novel strategies that impact cancer progression.

Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

In recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.