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Nature Communications Nov 2023The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly...
The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.
Topics: Humans; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Microbiota; Metagenome; Bacteria; Neoplasms
PubMed: 37973916
DOI: 10.1038/s41467-023-42997-7 -
Current Gastroenterology Reports Nov 2023This review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory... (Review)
Review
PURPOSE OF THE REVIEW
This review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory bowel disease (IBD).
RECENT FINDINGS
Several real-world studies and one clinical trial in children have demonstrated that proactive TDM, targeting higher exposure concentrations (> 5 µg/mL), can improve disease remission rates and enhance durability of the anti-TNF biologics. Recent data from both adult and pediatric IBD patients have revealed an association between a genetic polymorphism (HLA-DQA1*05) and the development of auto-drug antibodies. The impact of this association on clinical outcomes, considering more routine use proactive TDM and dose optimization in children, is still under investigation. Additionally, recent studies have identified potential inflammatory signatures and biomarkers that may serve as companion diagnostics for anti-TNF biologics. The effective management of anti-TNF therapies in children with IBD requires evidence-based precision dosing strategies, including routine TDM and proactive pharmacodynamic assessments.
Topics: Adult; Humans; Child; Tumor Necrosis Factor Inhibitors; Gastrointestinal Agents; Tumor Necrosis Factor-alpha; Inflammatory Bowel Diseases; Biological Products; Drug Monitoring; Infliximab
PubMed: 37695555
DOI: 10.1007/s11894-023-00895-4 -
Annual Review of Pharmacology and... Jan 2024I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have... (Review)
Review
I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis, mouse genetics, human genetics, and evolutionary genomics. Looking back, I think my career can be divided into four distinct research areas, which I summarize mostly chronologically in this article: () discovery and characterization of the AHR/CYP1 axis, () pharmacogenomics and genetic prediction of response to drugs and other environmental toxicants, () standardized drug-metabolizing gene nomenclature based on evolutionary divergence, and () discovery and characterization of the gene encoding the ZIP8 metal cation influx transporter. Collectively, all four topics embrace gene-environment interactions, hence the title of my autobiography.
Topics: Humans; Animals; Mice; Genomics; Membrane Transport Proteins; Pharmacogenetics; Physicians
PubMed: 37788491
DOI: 10.1146/annurev-pharmtox-022323-082311 -
Frontiers in Pharmacology 2023With the trend towards promoting personalised medicine (PM), the application of pharmacogenetics and pharmacogenomics (PGx) is of growing importance. For the purposes of...
With the trend towards promoting personalised medicine (PM), the application of pharmacogenetics and pharmacogenomics (PGx) is of growing importance. For the purposes of clinical trials, the inclusion of PGx is an additional tool that should be considered for improving our knowledge about the effectiveness and safety of new drugs. A search of available clinical trials containing pharmacogenetic and PGx information was conducted on ClinicalTrials.gov. The results show there has been an increase in the number of trials containing PGx information since the 2000 s, with particular relevance in the areas of Oncology (28.43%) and Mental Health (10.66%). Most of the clinical trials focus on treatment as their primary purpose. In those clinical trials entries where the specific genes considered for study are detailed, the most frequently explored genes are (especially in Mental Health and Pain), (in Hematology), (in Cardiology and Mental Health) and and (particularly prominent in Transplantation and Cardiology), among others. Researchers and clinicans should be trained in pharmacogenetics and PGx in order to be able to make a proper interpretation of this data, contributing to better prescribing decisions and an improvement in patients' care, which would lead to the performance of PM.
PubMed: 37927590
DOI: 10.3389/fphar.2023.1247088 -
Cancer Letters Jun 2023Tumor immunotherapy is a new therapeutic approach that has been evolving in the last decade and has dramatically changed the treatment options for cancer. Circular RNAs... (Review)
Review
Tumor immunotherapy is a new therapeutic approach that has been evolving in the last decade and has dramatically changed the treatment options for cancer. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with high stability, tissue-specific and cell-specific expression. There is growing evidence that circRNAs are involved in the regulation of both adaptive and innate immunity. They play important roles in tumor immunotherapy by affecting macrophage, NK and T cell function. The high stability and tissue specificity make them ideal candidate biomarkers for therapeutic effects. CircRNAs also represent one of promising targets or adjuvant for immunotherapy. Investigations in this field progress rapidly and provide essential support for the diagnosis, prognosis and treatment guidance of cancers in the future. In this review, we summarize the role of circRNAs on tumor immunity from the viewpoint of innate and adaptive immunity, and explore the role of circRNAs in tumor immunotherapy.
Topics: Humans; RNA, Circular; Biomarkers; Neoplasms; Adaptive Immunity; Immunotherapy
PubMed: 37146937
DOI: 10.1016/j.canlet.2023.216219 -
Pharmaceutics Oct 2023The modalities for prescribing a psychotropic (dose and choice of molecule) are currently unsatisfactory, which can lead to a lack of efficacy of the treatment... (Review)
Review
The modalities for prescribing a psychotropic (dose and choice of molecule) are currently unsatisfactory, which can lead to a lack of efficacy of the treatment associated with prolonged exposure of the patient to the symptoms of his or her illness and the side effects of the molecule. In order to improve the quality of treatment prescription, a part of the current biomedical research is dedicated to the development of pharmacogenetic tools for individualized prescription. In this guideline, we will present the genes of interest with level 1 clinical recommendations according to PharmGKB for the two major families of psychotropics: antipsychotics and antidepressants. For antipsychotics, there are and , and for antidepressants, , , and . The study will focus on describing the role of each gene, presenting the variants that cause functional changes, and discussing the implications for prescriptions in clinical practice.
PubMed: 38004520
DOI: 10.3390/pharmaceutics15112540