Sistema de Salut de Catalunya
Institut Català de la Salut
[Salazar J] Translational Medical Oncology Laboratory, Institut de Recerca Sant Pau (IR Sant Pau), Barcelona, Spain. [Arranz MJ] Research Laboratory Unit, Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. [Martin-Broto J] Medical Oncology Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Bautista F] Pediatric Hematology and Oncology Department, Hospital Niño Jesús, Madrid, Spain. Princess Maxima Centrum for Pediatric Cancer, Utrecht, The Netherlands. [Martínez-García J] Medical Oncology Department, Hospital Universitario Virgen de la Arrixaca, El Palmar, Spain. [Martínez-Trufero J] Medical Oncology Department, University Hospital Miguel Servet, Zaragoza, Spain. [Valverde C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
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.
Article
Published version
English
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
MDPI
Pharmaceutics;16(12)
https://doi.org/10.3390/pharmaceutics16121585
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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