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Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-032023-121106. Online ahead of print.ABSTRACTPharmacogenomics (PGx) enables personalized treatment for the prediction of drug response and to avoid adverse drug reactions. Currently, PGx mainly relies on the genetic information of absorption, distribution, metabolism, and excretion (ADME) targets such as drug-metabolizing enzymes or transporters to predict differences in the patient's phenotype. However, there is evidence that the phenotype-genotype concordance is limited. Thus, we discuss different phenotyping strategies using exogenous xenobiotics (e....
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Roman Tremmel Ute Hofmann Mathias Haag Elke Schaeffeler Matthias Schwab Source Type: research

Targeting Efferocytosis in Inflammaging
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-032723-110507. Online ahead of print.ABSTRACTRapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, ...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Ivan K H Poon Kodi S Ravichandran Source Type: research

Apathy and Motivation: Biological Basis and Drug Treatment
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-022423-014645. Online ahead of print.ABSTRACTApathy is a disabling syndrome associated with poor functional outcomes that is common across a broad range of neurological and psychiatric conditions. Currently, there are no established therapies specifically for the condition, and safe and effective treatments are urgently needed. Advances in the understanding of motivation and goal-directed behavior in humans and animals have shed light on the cognitive and neurobiological mechanisms contributing to apathy, providing an important foundation for the develo...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Harry Costello Masud Husain Jonathan P Roiser Source Type: research

From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-022123-104147. Online ahead of print.ABSTRACTThalidomide and its derivatives are powerful cancer therapeutics that are among the best-understood molecular glue degraders (MGDs). These drugs selectively reprogram the E3 ubiquitin ligase cereblon (CRBN) to commit target proteins for degradation by the ubiquitin-proteasome system. MGDs create novel recognition interfaces on the surface of the E3 ligase that engage in induced protein-protein interactions with neosubstrates. Molecular insight into their mechanism of action opens exciting opportunities to eng...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Vladas Oleinikovas Pablo Gainza Thomas Ryckmans Bernhard Fasching Nicolas H Thom ä Source Type: research

The Nocebo Effect
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-022723-112425. Online ahead of print.ABSTRACTAdverse nocebo responses can cause harm to patients and interfere with treatment adherence and effects in both clinic practice and clinical trials. Nocebo responses refer to negative outcomes to active medical treatments in clinical trials or practice that cannot be explained by the treatment's pharmacologic effects. Negative expectancies and nocebo effects are less known than placebo responses. Nocebo effects can be triggered by verbal suggestions, prior negative experiences, observation of others experienci...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Luana Colloca Source Type: research