oa Editorial [Hot Topic: Lipids in Cancer Cell Biology and Therapy Guest Editor: Jose C. Fernandez-Checa)]

Cancer-related morbidity is one of the leading causes of deaths in the world. Due to the social and health impact of cancer, research on cellular and molecular pathways leading to oncogenesis and carcinogenesis is one of the most active areas of biomedical investigation. Moreover, the uncovering of pathways that foster cancer growth and cell death resistance may also result in the development of more efficient therapeutic options for the treatment of cancer. In this special issue of Anti Cancer Agents in Medicinal Chemistry, a group of expert leaders summarize emerging evidence on the exciting role of cholesterol and sphingolipids (SLs) in the regulation of cancer cell biology and therapy. In addition to playing a key structural role in biological membranes, recent data have uncovered a critical function for cholesterol and SLs in the modulation of essential pathways involved in cancer cell biology. Particularly, ceramide and cholesterol regulate cell death pathways and hence play a crucial role in determining the susceptibility of cancer cells to current therapy, thus providing a rationale for novel therapeutic combinations. In this regard, Ballereau et al., examine the role of ceramide functionalization at the C1-OH position as a promising approach for cancer therapy (1). Although ceramide is well recognized as a proapoptotic lipid moiety, ceramide metabolism in cancer cells is altered giving rise to other metabolites involved in tumor progression and drug resistance. The authors review data indicating the key role of enzymes that modify ceramide at the C1-OH position generating other biologically important SLs in cancer, such as sphingomyelin, ceramide-1-phosphate or glucosylceramide. Thus, modulating these enzymes may open novel opportunities for improving current chemotherapy. In the review by Mullen and Obeid, the authors provide an extensive overview of the role of ceramide and apoptosis (2). In particular, the authors explore enigmatic connections between sphingolipid metabolism and programmed cell death, particularly focussing on the role of de novo sphingolipid synthesis and sphingosine salvage in producing proapoptotic ceramide, involving mitochondrial membrane permeabilization. Due to the critical role of mitochondria in the regulation of cell death pathways this connection may be of relevance in regulating cancer cells susceptibility to apoptosis and chemotherapy......