Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy

• Lucia Osorio ^[11] ; Tatiana P. Grazioso ^[12] ; Guillermo de Velasco ^[1] ; Olatz Etxaniz ^[13] ; José Luis Pérez Gracia ^[2] ; Álvaro Pinto ^[3] ; Ignacio Durán ^[4] ; Enrique Grande ^[14] ; Pablo Borrega Garcia ^[15] ; Martín Lázaro ^[5] ; Laura Rodriguez ^[6] ; María Laura Villalobos ^[7] ; Lourdes García ^[16] ; Andrés Cuellar ^[8] ; María Pilar Solís Hernández ^[9] ; Cristina Pernaut ^[10] ; Juan Francisco Rodríguez Moreno ^[12] ; Cristina Rodríguez Antona ^[17] ; Jesús García Donas ^[12]
  1. [1] Hospital Universitario 12 de Octubre

     Hospital Universitario 12 de Octubre

     Madrid, España

     
  2. [2] Clínica Universitaria de Navarra

     Clínica Universitaria de Navarra

     Pamplona, España

     
  3. [3] Hospital Universitario La Paz

     Hospital Universitario La Paz

     Madrid, España

     
  4. [4] Hospital Universitario Marqués de Valdecilla

     Hospital Universitario Marqués de Valdecilla

     Santander, España

     
  5. [5] Hospital Álvaro Cunqueiro

     Hospital Álvaro Cunqueiro

     Vigo, España

     
  6. [6] Hospital de Fuenlabrada

     Hospital de Fuenlabrada

     Fuenlabrada, España

     
  7. [7] Hospital Universitario Príncipe de Asturias

     Hospital Universitario Príncipe de Asturias

     Alcalá de Henares, España

     
  8. [8] Institute Catalá Oncología

     Institute Catalá Oncología

     Barcelona, España

     
  9. [9] Hospital Universitario Central de Asturias

     Hospital Universitario Central de Asturias

     Oviedo, España

     
  10. [10] Hospital Severo Ochoa

      Hospital Severo Ochoa

      Madrid, España

      
  11. [11] Servicio de Urología, Urología Hospitalaria, Hospital HM La Rosaleda, Santiago de Compostela, Spain
  12. [12] Instituto de Investigación Sanitaria HM Hospitales (IISHM), Madrid, Spain
  13. [13] Grupo de Investigación Aplicada en Oncología de Badalona (B·ARGO), Hospital Germá Trials I Pujol, Barcelona, Spain
  14. [14] Medical Oncology Department, MD Anderson Cancer Center Madrid, Madrid, Spain
  15. [15] Hospital Universitario de Cáceres, Cáceres, Spain
  16. [16] Hospital de Segovia, Segovia, Spain
  17. [17] Pharmacogenomics and Tumor Biomarkers Group, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC/UAM, Madrid, Spain

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 27, Nº. 5, 2025, págs. 2241-2255
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Background and purpose Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard frst-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to signifcant toxicity. However, a subgroup of patients has shown responsiveness to VEGFR tyrosine-kinase inhibitors (TKIs) in monotherapy, leading to the question of whether employing combination therapies can signifcantly enhance overall survival in all patients over monotherapy. Thus, we aim to identify gene expression signatures that can predict TKI response within subpopulations that might beneft from single-agent therapies, to minimize unnecessary exposure to combination therapies and their associated toxicities, as well as to discover new potential therapeutic targets to improve ccRCC treatment. Based on prior data, the androgen receptor (AR) might meet both conditions.

    Patients and methods We evaluated the association between AR expression, assessed through NanoString® technologyderived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with frst-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis.

    Results Higher AR-expression correlates signifcantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identifed a gene set signature associated with AR-overexpression and several genes involved in angiogenesis and transcriptional targets of the hypoxia-inducible factor, a cornerstone of ccRCC.

    Conclusions AR-overexpression and its association with other genes could favor a transcriptomic signature set to aid in identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.