Sistema de Salut de Catalunya
Institut Català de la Salut
[Juliachs M, Pujals M, Bellio C, Meo-Evoli N, Duran JM, Parés M, Suñol A, Méndez O, Canals F] Vall d’Hebron Institut of Oncology (VHIO), Barcelona, Spain. [Zamora E, Saura C] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Sánchez-Pla A] Genetics Microbiology and Statistics Department, Universitat de Barcelona, Barcelona, Spain. Unitat d'Estadística i Bioinformàtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Villanueva J] Vall d’Hebron Institut of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-06-06T08:01:22Z
2023-06-06T08:01:22Z
2022-08-10
Breast cancer; Response biomarkers; Secretome
Càncer de mama; Biomarcadors de resposta; Secretoma
Cáncer de mama; Biomarcadores de respuesta; Secretoma
There is a great need for non-invasive tools that inform of an early molecular response to cancer therapeutic treatment. Here, we tested the hypothesis that proteolytically resistant proteins could be candidate circulating tumor biomarkers for cancer therapy. Proteins resistant to proteolysis are drastically under-sampled by current proteomic workflows. These proteins could be reliable sensors for the response to therapy since they are likely to stay longer in circulation. We selected manganese superoxide dismutase (SOD2), a mitochondrial redox enzyme, from a screening of proteolytic resistant proteins in breast cancer (BC). First, we confirmed the robustness of SOD2 and determined that its proteolytic resistance is mediated by its quaternary protein structure. We also proved that the release of SOD2 upon chemotherapy treatment correlates with cell death in BC cells. Then, after confirming that SOD2 is very stable in human serum, we sought to measure its circulating levels in a cohort of BC patients undergoing neoadjuvant therapy. The results showed that circulating levels of SOD2 increased when patients responded to the treatment according to the tumor shrinkage during neoadjuvant chemotherapy. Therefore, the measurement of SOD2 levels in plasma could improve the non-invasive monitoring of the therapeutic treatment in breast cancer patients. The identification of circulating biomarkers linked to the tumor cell death induced by treatment could be useful for monitoring the action of the large number of cancer drugs currently used in clinics. We envision that our approach could help uncover candidate tumor biomarkers to measure a tumor’s response to cancer therapy in real time by sampling the tumor throughout the course of treatment.
This work was funded by Servier.
Article
Published version
English
Mama - Càncer - Tractament; Marcadors tumorals; Medicaments antineoplàstics - Ús terapèutic; DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy; ANATOMY::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor; CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento combinado::tratamiento neoadyuvante; ANATOMÍA::células::células cultivadas::línea celular::línea celular tumoral; COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales
MDPI
Cancers;14(16)
https://doi.org/10.3390/cancers14163858
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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