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Identification of ADME genes polymorphic variants linked to trastuzumab-induced cardiotoxicity in breast cancer patients: Case series of mono-institutional experience

التفاصيل البيبلوغرافية
العنوان: Identification of ADME genes polymorphic variants linked to trastuzumab-induced cardiotoxicity in breast cancer patients: Case series of mono-institutional experience
المؤلفون: Nicoletta Staropoli, Francesca Scionti, Valentina Farenza, Federica Falcone, Francesco Luciano, Maria Renne, Maria Teresa Di Martino, Domenico Ciliberto, Ludovica Tedesco, Antonella Crispino, Caterina Labanca, Maria Cucè, Stefania Esposito, Giuseppe Agapito, Mario Cannataro, Pierfrancesco Tassone, Pierosandro Tagliaferri, Mariamena Arbitrio
المصدر: Biomedicine & Pharmacotherapy, Vol 174, Iss , Pp 116478- (2024)
بيانات النشر: Elsevier, 2024.
سنة النشر: 2024
المجموعة: LCC:Therapeutics. Pharmacology
مصطلحات موضوعية: ADME, absorption, distribution, metabolism and excretion genes, ADME genes polymorphic variants, trastuzumab, Therapeutics. Pharmacology, RM1-950
الوصف: Background: Long-term survival induced by anticancer treatments discloses emerging frailty among breast cancer (BC) survivors. Trastuzumab-induced cardiotoxicity (TIC) is reported in at least 5% of HER2+BC patients. However, TIC mechanism remains unclear and predictive genetic biomarkers are still lacking. Interaction between systemic inflammation, cytokine release and ADME genes in cancer patients might contribute to explain mechanisms underlying individual susceptibility to TIC and drug response variability. We present a single institution case series to investigate the potential role of genetic variants in ADME genes in HER2+BC patients TIC experienced. Methods: We selected data related to 40 HER2+ BC patients undergone to DMET genotyping of ADME constitutive variant profiling, with the aim to prospectively explore their potential role in developing TIC. Only 3 patients (“case series”), who experienced TIC, were compared to 37 “control group” matched patients cardiotoxicity-sparing. All patients underwent to left ventricular ejection fraction (LVEF) evaluation at diagnosis and during anti-HER2 therapy. Each single probe was clustered to detect SNPs related to cardiotoxicity. Results: In this retrospective analysis, our 3 cases were homogeneous in terms of clinical-pathological characteristics, trastuzumab-based treatment and LVEF decline. We identified 9 polymorphic variants in 8 ADME genes (UGT1A1, UGT1A6, UGT1A7, UGT2B15, SLC22A1, CYP3A5, ABCC4, CYP2D6) potentially associated with TIC. Conclusion: Real-world TIC incidence is higher compared to randomized clinical trials and biomarkers with potential predictive value aren’t available. Our preliminary data, as proof of concept, could suggest a predictive role of pharmacogenomic approach in the identification of cardiotoxicity risk biomarkers for anti-HER2 treatment.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 0753-3322
24511943
Relation: http://www.sciencedirect.com/science/article/pii/S0753332224003627; https://doaj.org/toc/0753-3322
DOI: 10.1016/j.biopha.2024.116478
URL الوصول: https://doaj.org/article/525912e00ae24511943ab9978d60570d
رقم الأكسشن: edsdoj.525912e00ae24511943ab9978d60570d
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:07533322
24511943
DOI:10.1016/j.biopha.2024.116478