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Pharmacogenomics Beyond Single Common Genetic Variants: The Way Forward
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-051921-091209. Online ahead of print.ABSTRACTInterindividual variability in genes encoding drug-metabolizing enzymes, transporters, receptors, and human leukocyte antigens has a major impact on a patient's response to drugs with regard to efficacy and safety. Enabled by both technological and conceptual advances, the field of pharmacogenomics is developing rapidly. Major progress in omics profiling methods has enabled novel genotypic and phenotypic characterization of patients and biobanks. These developments are paralleled by advances in machine learni...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Volker M Lauschke Yitian Zhou Magnus Ingelman-Sundberg Source Type: research

High-Throughput Screening to Advance In Vitro Toxicology: Accomplishments, Challenges, and Future Directions
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-112122-104310. Online ahead of print.ABSTRACTTraditionally, chemical toxicity is determined by in vivo animal studies, which are low throughput, expensive, and sometimes fail to predict compound toxicity in humans. Due to the increasing number of chemicals in use and the high rate of drug candidate failure due to toxicity, it is imperative to develop in vitro, high-throughput screening methods to determine toxicity. The Tox21 program, a unique research consortium of federal public health agencies, was established to address and identify toxicity concern...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Caitlin Lynch Srilatha Sakamuru Masato Ooka Ruili Huang Carleen Klumpp-Thomas Paul Shinn David Gerhold Anna Rossoshek Sam Michael Warren Casey Michael F Santillo Suzanne Fitzpatrick Russell S Thomas Anton Simeonov Menghang Xia Source Type: research

LP(a): Structure, Genetics, Associated Cardiovascular Risk, and Emerging Therapeutics
Annu Rev Pharmacol Toxicol. 2023 Jul 28. doi: 10.1146/annurev-pharmtox-031023-100609. Online ahead of print.ABSTRACTLipoprotein(a) [Lp(a)] is a molecule bound to apolipoprotein(a) with some similarity to low-density lipoprotein cholesterol (LDL-C), which has been found to be a risk factor for cardiovascular disease (CVD). Lp(a) appears to induce inflammation, atherogenesis, and thrombosis. Approximately 20% of the world's population has increased Lp(a) levels, determined predominantly by genetics. Current clinical practices for the management of dyslipidemia are ineffective in lowering Lp(a) levels. Evolving RNA-based ther...
Source: Annual Review of Pharmacology and Toxicology - July 28, 2023 Category: Drugs & Pharmacology Authors: Erfan Tasdighi Rishav Adhikari Omar Almaadawy Thorsten M Leucker Michael J Blaha Source Type: research

Addressing Ancestry and Sex Bias in Pharmacogenomics
Annu Rev Pharmacol Toxicol. 2023 Jul 14. doi: 10.1146/annurev-pharmtox-030823-111731. Online ahead of print.ABSTRACTThe association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied,...
Source: Annual Review of Pharmacology and Toxicology - July 14, 2023 Category: Drugs & Pharmacology Authors: Manuel Corpas Moneeza K Siddiqui Opeyemi Soremekun Rohini Mathur Dipender Gill Segun Fatumo Source Type: research