Academic Journal

Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy

التفاصيل البيبلوغرافية
العنوان: Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy
المؤلفون: Anna C. Virgili Manrique, Juliana Salazar, María Jesús Arranz, Silvia Bagué, Ruth Orellana, Antonio López-Pousa, Paula Cerdà, Isidre Gracia, Katarina Majercakova, Ana Peiró, Laura Trullols, Manuel Fernández, Sandra Valverde, María Jesús Quintana, Olga Bell, Alícia Artigas-Baleri, Ana Sebio
المصدر: Journal of Personalized Medicine; Volume 12; Issue 4; Pages: 618
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2022
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: soft tissue sarcoma, neoadjuvant, pharmacogenetics, anthracyclines, ifosfamide, ALDH1A1, ABCC2, ABCB1
الوصف: Neoadjuvant chemotherapy based on anthracyclines and ifosfamide for high-risk soft tissue sarcomas (STS) of the extremities and trunk is a controversial treatment option. There are substantial interindividual differences in clinical outcomes in patients treated with neoadjuvant chemotherapy. The aim of this study was to evaluate, as biomarkers, polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, or drug targets and their association with toxicity and survival in STS patients treated with neoadjuvant chemotherapy. We analysed variants in genes involved in anthracycline metabolism (ABCB1, ABCC2, NQO1, CBR3, and SLC22A16) and in ifosfamide catabolism (ALDH1A1) in 79 treated patients. Two genes showed significant association after adjusted multivariate analysis: ABCC2 and ALDH1A1. In patients treated with anthracyclines, ABCC2 rs3740066 was associated with risk of febrile neutropenia (p = 0.031), and with decreased overall survival (OS) (p = 0.024). ABCC2 rs2273697 was associated with recurrence-free survival (RFS) (p = 0.024). In patients treated with ifosfamide, ALDH1A1 rs3764435 was associated with RFS (p = 0.046). Our pharmacogenetic study shows for the first time that variants in genes regulating the metabolism of neoadjuvant chemotherapy may be helpful to predict toxicity and survival benefit in high-risk STS treated with neoadjuvant chemotherapy. Further validation studies are needed to establish their clinical utility.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
Relation: Pharmacogenetics; https://dx.doi.org/10.3390/jpm12040618
DOI: 10.3390/jpm12040618
الاتاحة: https://doi.org/10.3390/jpm12040618
Rights: https://creativecommons.org/licenses/by/4.0/
رقم الانضمام: edsbas.46B594C3
قاعدة البيانات: BASE