AI Article Synopsis
- - Paclitaxel, a widely used chemotherapy drug, is effective in treating various cancers but is associated with significant neurotoxicity and other adverse effects, prompting research into its safety profile.
- - The review discusses mechanisms and risk factors behind paclitaxel-induced toxicities, focusing on pharmacogenomic biomarkers, with specific attention to genes linked to neuro-sensitivity as promising candidates for further investigation.
- - Genome-wide studies have identified various candidate genes related to neuro-sensitivity, suggesting future research should explore these genes and their multifactorial influences on toxicity rather than relying solely on pharmacokinetic pathways, which have shown inconsistent results.
Article Abstract
: Paclitaxel is a microtubule stabilizer that is currently one of the most utilized chemotherapeutic agents. Its efficacy in breast, uterine, lung and other neoplasms made its safety profile enhancement a subject of great interest. Neurotoxicity is the most common paclitaxel-associated toxicities. In addition, hypersensitivity reactions, hematological, gastrointestinal, and cardiac toxicities are all encountered.: The current review explores paclitaxel-induced toxicities mechanisms and risk factors. Studies investigating these toxicities pharmacogenomic biomarkers are reviewed and summarized. There is a limited margin of consistency between the retrieved associations. Variants in genes related to neuro-sensitivity are the most promising candidates for future studies.: Genome-wide association studies highlighted multiple-candidate biomarkers relevant to neuro-sensitivity. Most of the identified paclitaxel-neurotoxicity candidate genes are derived from congenital neuropathy and diabetic-induced neurotoxicity pathways. Future studies should explore these sets of genes while considering the multifactorial nature of paclitaxel-induced neurotoxicity. In the absence of certain paclitaxel-toxicity biomarkers, future research should avoid earlier studies' caveats. Genes in paclitaxel's pharmacokinetic pathways could not provide consistent results in any of its associated toxicities. There is a need to dig deeper into toxicity-development mechanisms and personal vulnerability factors, rather than targeting only the genes suspected to affect drug exposure.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/17425255.2021.1943358 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Appraisal of the evidence linking hereditary α-tryptasemia with mast cell disorders, hypermobility and dysautonomia.
Allergy Asthma Proc
January 2025
From the Division of Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, California and.
Since its first description more than a decade ago, our understanding of the clinical impact of hereditary alpha-tryptasemia has continued to evolve. First considered to be a genetic disorder with a subset of patients having a syndromic presentation composed of connective tissue abnormalities, symptoms of autonomic dysfunction, and findings of mast cell activation, we now know that hereditary alpha-tryptasemia is a common genetic trait and modifier of mast cell-mediated reactions. More recent studies have shown some previously held associations with congenital hypermobility and postural orthostatic tachycardia syndrome (POTS) to be lacking, and illuminated previously unappreciated associations with clonal and nonclonal mast cell disorders.
View Article and Find Full Text PDFEfficacy of parenteral bronchodilators on ventilatory outcomes in pediatric critical asthma: a national cohort study.
Allergy Asthma Proc
January 2025
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
To evaluate the association of parenteral epinephrine and terbutaline use on ventilatory support in children admitted to the intensive care unit (ICU) with critical asthma in the United States. Data were obtained from the Pediatric Health Information System data base for children ages 2 to 18 years admitted to the ICU with a diagnosis of asthma exacerbation from January 1, 2016, to December 31, 2023. The primary outcomes included noninvasive ventilation (NIV) and/or invasive mechanical ventilation (IMV) use after receipt of terbutaline and/or epinephrine.
View Article and Find Full Text PDFStudies of methylated CpG ODN from subsp. in a murine model: Implications for treatment of human allergic disease.
Allergy Asthma Proc
January 2025
From the Department of Microbiology-Immunology, Georgetown University Medical Center, Washington, D.C.
Allergen immunotherapy (AIT) is currently the most effective immunologic form of treatment for patients with atopic allergic diseases commonly used by allergist/immunologists to reduce allergic symptoms by gradually desensitizing the immune system to specific allergens. Currently, the primary mechanism of AIT emphasizes the crucial role of immune regulation, which involves a shift from a T-helper type 2 (Th2) cell response, which promotes allergy, to a T-regulatory (Treg) cell population, which inhibits the allergic inflammatory response through the production of immunosuppressive cytokines interleukin 10 and transforming growth factor β, which play pivotal roles in suppressing the allergic reaction. In a series of previous in vitro and in vivo experiments, we have demonstrated the capacity of synthetic methylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) moieties as well as methylated genomic DNA ODN motifs from Bifidobacterium longum subspecies infantis to activate Treg cell differentiation in contrast to the unmethylated ODN moiety, which promotes proinflammatory responses driven by Th17-mediated responses.
View Article and Find Full Text PDFPatient-derived response estimates from zero-passage organoids of luminal breast cancer.
Breast Cancer Res
December 2024
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, 22908, USA.
Background: Primary luminal breast cancer cells lose their identity rapidly in standard tissue culture, which is problematic for testing hormone interventions and molecular pathways specific to the luminal subtype. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Our goal was to adapt short-term organoids of luminal breast cancer for parallel testing of genetic and pharmacologic perturbations.
View Article and Find Full Text PDFHealth checks for autistic adults: study protocol for a cluster randomised controlled trial.
Trials
December 2024
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Background: Autistic people commonly have physical and mental health conditions. They also frequently experience barriers to accessing healthcare, contributing to problems identifying and treating health conditions. These factors may lead to increased and earlier morbidity and lower average life expectancy for autistic people.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!