2026-04-17T12:11:56Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4706122025-10-17T15:23:51Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Virgili Manrique, Anna Cristina author Salazar, Juliana author Arranz, María Jesús author Bagué Rosell, Sílvia author Orellana Fernández, Ruth author López Pousa, Antonio author Cerdà, Paula author Gracia, Isidro author Majercakova, Katarina author Peiró, Ana author Trullols, L. author Fernández Garrido, Manuel author Valverde, Sandra author Quintana Ruiz, Maria Jesús author Bell, Olga author Artigas-Baleri, Alícia author Sebio, Ana author Universitat Autònoma de Barcelona author 2022 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 sub-stantial interindividual differences in clinical outcomes in patients treated with neoadjuvant chem-otherapy. 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 es-tablish their clinical utility. Soft tissue sarcoma Neoadjuvant Pharmacogenetics Anthracyclines Ifosfamide ALDH1A1 ABCC2 ABCB1 Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy