2026-04-13T06:37:43Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/125102025-02-04T00:37:35Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Salazar, Juliana
author
Arranz, Maria J
author
BAUTISTA, FRANCISCO JOSE
author
Martin-Broto, Javier
author
Martinez-Garcia, Jeronimo
author
Martinez-Trufero, Javier
author
Valverde, Claudia María
2025-02-04T00:37:35Z
2025-02-04T00:37:35Z
2025-01-31T10:52:58Z2025-01-31T10:52:58Z2024-12-12
http://hdl.handle.net/11351/12510
Neoadjuvant chemotherapy; Osteosarcoma; PharmacogenomicsQuimioterapia neoadyuvante; Osteosarcoma; FarmacogenómicaQuimioteràpia neoadjuvant; Osteosarcoma; FarmacogenòmicaBackground: Osteosarcoma is a rare disease, but it is the most frequent malignant bone tumor. Primary treatment consists of preoperative MAP (methotrexate (MTX), doxorubicin and cisplatin) chemotherapy followed by surgery and adjuvant chemotherapy. Pathological response to preoperative chemotherapy is one of the most important prognostic factors, but molecular biomarkers are lacking. Additionally, chemotherapy-induced toxicity might jeopardize treatment completion. We evaluated variants in genes involved in DNA repair and drug metabolism pathways as predictors of response to MAP-based treatment. Material and Methods: Germline polymorphisms in MTHFR, SLC19A1, ABCB1, ABCC2, ABCC3, ERCC1, ERCC2 and GSTP1 genes were determined for association studies in 69 patients diagnosed with localized osteosarcoma who enrolled in the prospective GEIS-33 trial. P-glycoprotein expression in tumor tissue was also analyzed. Results: In the multivariate analysis, the ABCC2 rs2273697 (odds ratio [OR] 12.3, 95% CI 2.3–66.2; p = 0.003) and ERCC2 rs1799793 (OR 9.6, 95% CI 2.1–43.2; p = 0.003) variants were associated with poor pathological response. P-glycoprotein expression did not correlate with pathological response. The ABCB1 rs1128503 (OR 11.4, 95% CI 2.2–58.0; p = 0.003) and ABCC3 rs4793665 (OR 12.0, 95% CI 2.1–70.2; p = 0.006) variants were associated with MTX grade 3–4 hepatotoxicity. Conclusions: Our findings add to the evidence that genetic variants in the ABC transporters and DNA-repair genes may serve as predictive biomarkers for MAP chemotherapy and contribute to treatment personalization.This research was funded by the Spanish Group of Sarcoma Research (GEIS). Funding identifier: Translational research projects by young researchers 2017.
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Quimioteràpia combinada
Ossos - Càncer - Tractament
Osteosarcoma - Càncer - Tractament
Osteosarcoma - Càncer - Cirurgia
Farmacogenòmica
DISCIPLINES AND OCCUPATIONS::Natural Science Disciplines::Biological Science Disciplines::Biology::Genetics::Pharmacogenetics
DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Connective Tissue::Neoplasms, Bone Tissue::Osteosarcoma
Other subheadings::Other subheadings::Other subheadings::/drug therapy
DISEASES::Neoplasms::Neoplasms by Site::Bone Neoplasms
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Chemotherapy, Adjuvant
DISCIPLINAS Y OCUPACIONES::disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::biología::genética::farmacogenética
ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido conjuntivo::neoplasias de tejido óseo::osteosarcoma
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias óseas
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::quimioterapia adyuvante
Pharmacogenetics of Neoadjuvant MAP Chemotherapy in Localized Osteosarcoma: A Study Based on Data from the GEIS-33 Protocol
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion