2026-04-14T05:06:19Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/125102025-02-04T00:37:35Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc 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 author 2025-01-31T10:52:58Z 2025-01-31T10:52:58Z 2024-12-12 Neoadjuvant chemotherapy; Osteosarcoma; Pharmacogenomics Quimioterapia neoadyuvante; Osteosarcoma; Farmacogenómica Quimioteràpia neoadjuvant; Osteosarcoma; Farmacogenòmica Background: 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. http://hdl.handle.net/11351/12510 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