Reprogramming of metabolic priorities promotes tumor progression. Our understanding of the Warburg effect, based on studies of cultured cancer cells, has evolved to a more complex understanding of tumor metabolism within an ecosystem that provides and catabolizes diverse nutrients provided by the local tumor microenvironment. Recent studies have illustrated that heterogeneous metabolic changes occur at the level of tumor type, tumor subtype, within the tumor itself, and within the tumor microenvironment. Thus, altered metabolism occurs in cancer cells and in the tumor microenvironment (fibroblasts, immune cells and fat cells). Herein we describe how these growth advantages are obtained through either “convergent” genetic changes, in which common metabolic properties are induced as a final common pathway induced by diverse oncogene factors, or “divergent” genetic changes, in which distinct factors lead to subtype-selective phenotypes and thereby tumor heterogeneity. Metabolic heterogeneity allows subtyping of cancers and further metabolic heterogeneity occurs within the same tumor mass thought of as “microenvironmental metabolic nesting”. Furthermore, recent findings show that mutations of metabolic genes arise in the majority of tumors providing an opportunity for the development of more robust metabolic models of an individual patient’s tumor. The focus of this review is on the mechanisms governing this metabolic heterogeneity in breast cancer.

Sexual dimorphism is not only noticed in the prevalence of many diseases, but also in multiple physiological functions in the body. This review has summarized findings from published literature on the sex differences of the pathophysiology and pharmacology of the lower urinary tract (LUT) of humans and animals. Sex differences have been found in several key areas of the LUT, such as overactive bladder, expression and function of neurotransmitter receptors in the bladder and urethra, and micturition patterns in humans and animals. It is anticipated that this review will not only evoke renewed interest for further research on the mechanism of sex differences in the pathophysiology of the LUT (especially for overactive bladder), but might also open up the possibilities for gender-based drug development by pharmaceutical industries in order to find separate cures for men and women with diseases of the LUT.

Several physiopathologic conditions lead to the manifestation of overactive bladder (OAB). These conditions include ageing, diabetes mellitus, bladder outlet obstruction, spinal cord injury, stroke and brain injury, Parkinson's disease, multiple sclerosis, interstitial cystitis, stress and depression. This review has discussed research findings in human and animal studies conducted on the above conditions. Several structural and functional changes under these conditions have not only been observed in the lower urinary tract, but also in the brain and spinal cord. Significant changes were observed in the following areas: neurotransmitters, prostaglandins, nerve growth factor, Rho-kinase, interstitial cells of Cajal, and ion and transient receptor potential channels. Interestingly, alterations in these areas showed great variation in each of the conditions of the OAB, suggesting that the pathophysiology of the OAB might be different in each condition of the disease. It is anticipated that this review will be helpful for further research on new and specific drug development against OAB.