Immunogenic cell death and DAMPs in cancer therapy

Although it was thought that apoptotic cells, when rapidly phagocytosed, underwent a silent death that did not trigger an immune response, in recent years a new concept of immunogenic cell death (ICD) has emerged. The immunogenic characteristics of ICD are mainly mediated by damage-associated molecular patterns (DAMPs), which include surface-exposed calreticulin (CRT), secreted ATP and released high mobility group protein B1 (HMGB1). Most DAMPs can be recognized by pattern recognition receptors (PRRs). In this Review, we discuss the role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and the effect of therapy-resistant cancer microevolution on ICD

Phosphate and FGF-23 homeostasis after kidney transplantation

Dysregulated phosphate metabolism is a common consequence of chronic kidney disease, and is characterized by a high circulating level of fibroblast growth factor (FGF)-23, hyperparathyroidism, and hyperphosphataemia. Kidney transplantation can elicit specific alterations to phosphate metabolism that evolve over time, ranging from severe hypophosphataemia (1.50 mmol/l) and high FGF-23 levels. The majority of renal transplant recipients develop hypophosphataemia during the first 3 months after transplantation as a consequence of relatively slow adaptation of FGF-23 and parathyroid hormone levels to restored renal function, and the influence of immunosuppressive drugs. By 3-12 months after transplantation, phosphate homeostasis is at least partially restored in the majority of recipients, which is paralleled by a substantially reduced risk of cardiovascular-associated morbidity and mortality compared with the pre-transplantation setting. Many renal transplant recipients, however, exhibit persistent abnormalities in phosphate homeostasis, which is often due to multifactorial causes, and may contribute to adverse outcomes on the cardiovascular system, kidney, and bone. Dietary and pharmacologic interventions might improve phosphate homeostasis in renal transplant recipients, but additional insight into the pathophysiology of transplantation-associated abnormalities in phosphate homeostasis is needed to further optimize disease management and improve prognosis for renal transplant recipients

Mechanisms of drug combinations: Interaction and network perspectives

10.1038/nrd2683Nature Reviews Drug Discovery82111-12