In the area of drug development and clinical pharmacotherapy, a profound understanding of the pharmacokinetics and potential adverse reactions associated with the drug under investigation is paramount. Essential to this endeavor is a comprehensive understanding about interindividual variations in absorption, distribution, metabolism, and excretion (ADME) genetics and the predictive capabilities of in vitro systems, shedding light on metabolite formation and the risk of adverse drug reactions (ADRs). Both the domains of pharmacogenomics and the advancement of in vitro systems are experiencing rapid expansion. Here we present an update on these burgeoning fields, providing an overview of their current status and illuminating potential future directions. SIGNIFICANCE STATEMENT: There is very rapid development in the area of pharmacogenomics and in vitro systems for predicting drug pharmacokinetics and risk for adverse drug reactions. We provide an update of the current status of pharmacogenomics and developed in vitro systems on these aspects aimed to achieve a better personalized pharmacotherapy.
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http://dx.doi.org/10.1124/dmd.123.001302 | DOI Listing |
Funct Integr Genomics
January 2025
Institute of Infectious Diseases, Guangdong Province, Guangzhou Eighth People's Hospital, Guangzhou Medical University, 8 Huaying Road, Baiyun District, Guangzhou, 510440, China.
Hepatocellular carcinoma (HCC) remains a malignant and life-threatening tumor with an extremely poor prognosis, posing a significant global health challenge. Despite the continuous emergence of novel therapeutic agents, patients exhibit substantial heterogeneity in their responses to anti-tumor drugs and overall prognosis. The pentose phosphate pathway (PPP) is highly activated in various tumor cells and plays a pivotal role in tumor metabolic reprogramming.
View Article and Find Full Text PDFSmall
January 2025
School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China.
Covalent organic frameworks (COFs), known for their exceptional in situ encapsulation and precise release capabilities, are emerging as pioneering drug delivery systems. This study introduces a hypoxia-responsive COF designed to encapsulate the chemotherapy drug gambogic acid (GA) in situ. Bimetallic gold-palladium islands were grown on UiO-66-NH (UiO) to form UiO@Au-Pd (UAPi), which were encapsulated with GA through COF membrane formation, resulting in a core-shell structure (UAPiGC).
View Article and Find Full Text PDFMol Ther
January 2025
Department of Biology, Concordia University, 7141 Sherbrooke St. W H4B 1R6, Montreal, Canada; Department of Physics, Concordia University, 7141 Sherbrooke St. W H4B 1R6, Montreal, Canada. Electronic address:
CRISPR-Cas9 ribonucleoproteins (RNPs) have been heavily considered for gene therapy due to their high on-target efficiency, rapid activity and lack of insertional mutagenesis relative to other CRISPR-Cas9 delivery formats. Genetic diseases such as hypertrophic cardiomyopathy currently lack effective treatment strategies and are prime targets for CRISPR-Cas9 gene editing technology. However, current in-vivo delivery strategies for Cas9 pose risks of unwanted immunogenic responses.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Gastroenterology, Endocrinology, Infectious Diseases and Metabolism, University Hospital Marburg, 35043 Marburg, Germany.
Background: Most spheroid models use size measurements as a primary readout parameter; some models extend analysis to T cell infiltration or perform caspase activation assays. However, to our knowledge, T cell motility analysis is not regularly included as an endpoint in imaging studies on cancer spheroids.
Methods: Here, we intend to demonstrate that motility analysis of macrophages and T cells is a valuable functional endpoint for studies on molecular interventions in the tumor microenvironment.
Cancers (Basel)
December 2024
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis School of Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA 95817, USA.
Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted therapies, immunotherapies, antibody-drug conjugates, and emerging investigational treatments.
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