Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy
Por:
Manrique, ACV, Salazar, J, Arranz, MJ, Bague, S, Orellana, R, Lopez-Pousa, A, Cerda, P, Gracia, I, Majercakova, K, Peiro, A, Trullols, L, Fernandez, M, Valverde, S, Quintana, MJ, Bell, O, Artigas-Baleri, A, Sebio, A
Publicada:
1 abr 2022
Resumen:
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.
Filiaciones:
Manrique, ACV:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Univ Autonoma Barcelona, Dept Med, Barcelona 08035, Spain
Salazar, J:
Hosp Santa Creu & Sant Pau, Med Translat Oncol Lab, IIB St Pau, Barcelona 08041, Spain
Arranz, MJ:
Fundacio Docencia & Recerca Mutua Terrassa, Terrassa 08221, Spain
Bague, S:
Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08041, Spain
Orellana, R:
Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08041, Spain
Lopez-Pousa, A:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Cerda, P:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Gracia, I:
Hosp Santa Creu & Sant Pau, Orthopaed & Trauma Surg, Barcelona 08041, Spain
Majercakova, K:
Hosp Santa Creu & Sant Pau, Radiat Oncol, Barcelona 08041, Spain
Peiro, A:
Hosp Santa Creu & Sant Pau, Orthopaed & Trauma Surg, Barcelona 08041, Spain
Trullols, L:
Hosp Santa Creu & Sant Pau, Orthopaed & Trauma Surg, Barcelona 08041, Spain
Fernandez, M:
Hosp Santa Creu & Sant Pau, Plast & Reconstruct Surg, Barcelona 08041, Spain
Valverde, S:
Hosp Santa Creu & Sant Pau, Radiol Dept, Barcelona 08041, Spain
Quintana, MJ:
Hosp Santa Creu & Sant Pau, Epidemiol Dept, Barcelona 08041, Spain
Bell, O:
Hosp Santa Creu & Sant Pau, Med Translat Oncol Lab, IIB St Pau, Barcelona 08041, Spain
Artigas-Baleri, A:
Hosp Santa Creu & Sant Pau, IIB St Pau, Genet Dept, Barcelona 08041, Spain
Sebio, A:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Green Published, gold, Gold, Green
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