TY - JOUR AB - Identifying safe and effective CAR T cell targets in acute myeloid leukemia (AML) is challenging due to the disease's complexity and overlap with normal hematopoiesis. This review highlights advances in target discovery for AML, emphasizing innovative approaches. Structural surfaceomics identifies tumor-specific protein conformations, while AI-driven single-cell RNA sequencing integrates multi-source data to pinpoint optimal targets. Refined cell surface capture technology maps the AML surfaceome without relying on predefined antibodies. These strategies enhance CAR T cell specificity and minimize off-tumor effects, offering promising pathways for safer and more effective AML treatments and broader cancer therapies. AU - Hoffmann, G.V.* AU - Gottschlich, A.* AU - Subklewe, M.* AU - Kobold, S. C1 - 74303 C2 - 57428 CY - 125 London Wall, London, England TI - Novel approaches to CAR T cell target identification in acute myeloid leukemia. JO - Curr. Opin. Pharmacol. VL - 82 PB - Elsevier Sci Ltd PY - 2025 SN - 1471-4892 ER - TY - JOUR AB - Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies. AU - Molocea, C.-E. AU - Tsokanos, F.-F. AU - Herzig, S. C1 - 60004 C2 - 49164 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 101-116 TI - Exploiting common aspects of obesity and cancer cachexia for future therapeutic strategies. JO - Curr. Opin. Pharmacol. VL - 53 PB - Elsevier Sci Ltd PY - 2020 SN - 1471-4892 ER - TY - JOUR AB - Glucocorticoids (GCs) are widely used immunomodulators. They regulate gene expression by binding and activating the Glucocorticoid Receptor (GR), but underlying transcriptional mechanisms remain enigmatic. This review summarizes recent findings identifyingspecific GR-bound DNA sequences whose configuration may affect transcriptional output. Additional factors affecting GR's anti-inflammatory actions, including different chromatin states such as DNAse hypersensitive regions and histone marks will be discussed, together with the relevant transcriptional co-regulators and promoter/enhancer features. Furthermore, the involvement of non-coding RNAs such as lncRNAs, miRNAs and eRNAs adds another level of regulation to the GR's transcriptional activity. Characterizing and understanding these multiple mechanisms will be crucial for developing more targeted immunomodulatory therapies with reduced adverse effects such as obesity, diabetes and osteoporosis. AU - Syed, A.P. AU - Greulich, F. AU - Ansari, S.A. AU - Uhlenhaut, N.H. C1 - 59144 C2 - 48596 CY - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England SP - 35-44 TI - Anti-inflammatory glucocorticoid action: Genomic insights and emerging concepts. JO - Curr. Opin. Pharmacol. VL - 53 PB - Elsevier Sci Ltd PY - 2020 SN - 1471-4892 ER - TY - JOUR AB - Keratinocyte carcinoma (KC), previously also known as non-melanoma skin cancer, is the most common malignancy worldwide. It comprises basal cell carcinoma, squamous cell carcinoma (SCC), and actinic keratoses as carcinoma in situ or precursors of SCC. With solar ultraviolet radiation being the main risk factor, several countries have accepted KC as an occupational disease of outdoor professions. The prevalence in these high-risk groups is substantial, but awareness and preventive behavior remains inadequate. Parallel to the development of improved treatments, such as daylight photodynamic therapy and PD1 inhibitors for progressive KC, target-oriented prevention strategies are requisite if the global burden of KC is to be lowered. Health-related communication, internet search analysis, and telemedicine could be the key to addressing this issue. AU - Zink, A. C1 - 55297 C2 - 46247 SP - 19-23 TI - Trends in the treatment and prevention of keratinocyte carcinoma (non-melanoma skin cancer). JO - Curr. Opin. Pharmacol. VL - 46 PY - 2019 SN - 1471-4892 ER - TY - JOUR AB - Obesity results from the consumption of food in excess of bodily energy requirements, with the excess energy stored as adipose tissue. Sequelae of obesity, such as heart disease and type 2 diabetes, consistently rank among the top causes of death worldwide. The global prevalence of obesity highlights the urgency of understanding the mechanisms regulating hunger and satiety. Appetite, defined as the motivational drive to obtain food, is regulated by a complex neurocircuitry which integrates a variety of interoceptive signals to gauge nutritional state and guide appropriate levels of food-seeking. Here we review key recent developments in the identification of cell groups, neural circuits, endogenous and exogenous substances, and intracellular signaling pathways which drive hunger and satiety. We also consider particularly promising pharmacological targets for appetite modulation. AU - Heisler, L.K.* AU - Lam, D.D. C1 - 52277 C2 - 43884 CY - Oxford SP - 100-106 TI - An appetite for life: Brain regulation of hunger and satiety. JO - Curr. Opin. Pharmacol. VL - 37 PB - Elsevier Sci Ltd PY - 2017 SN - 1471-4892 ER - TY - JOUR AB - Traditionally, the development of novel therapeutics for metabolic diseases has relied mainly on high-throughput screening using biochemical or cell-based assays. While this approach represents a driving force in drug discovery, there is also a need to perform large-scale screens without disrupting inter-organ communication and tissue architecture, essential components for understanding the complexity of metabolic regulation and the identification of small molecules with appropriate biological activities in vivo. Hence, the zebrafish Danio rerio is gaining popularity in metabolic research and drug discovery, as this animal model allows screening of small molecules in the context of the whole-organism. Moreover, the zebrafish exhibits conserved function of the pancreas, liver and adipose tissue, which can be leveraged to identify novel targets in metabolic regulation, as well as to study the role of conserved genes associated with the risk of metabolic diseases in humans. Here we highlight recent advances in the identification of targets in metabolic regulation using the zebrafish as a model. AU - Kamel, M.* AU - Ninov, N. C1 - 51841 C2 - 43490 CY - Oxford SP - 41-50 TI - Catching new targets in metabolic disease with a zebrafish. JO - Curr. Opin. Pharmacol. VL - 37 PB - Elsevier Sci Ltd PY - 2017 SN - 1471-4892 ER -