Scientific publications
Retrospective study assessing the role of the androgen receptor in clear cell renal cell cancer patients treated with VEGFR inhibitors in monotherapy. Scientific Publications
Lucia Osorio 1 2 , Tatiana P Grazioso 2 3 4 , Guillermo de Velasco 5 , Olatz Etxaniz 6 , Jose Luis Pérez-Gracia 7 , Álvaro Pinto 8 , Ignacio Durán 9 , Enrique Grande 10 , Pablo Borrega Garcia 11 , Martín Lázaro 12 , Laura Rodriguez 13 , Maria Laura Villalobos 14 , Lourdes García 15 , Andrés Cuellar 16 , María Pilar Solís-Hernández 17 , Cristina Pernaut 18 , Juan Francisco Rodríguez-Moreno 2 3 4 , Cristina Rodriguez-Antona 19 20 , Jesús García-Donas 21 22 23
Background and purpose: Despite that incorporating antiangiogenic in combination with immune-checkpoint inhibitors as the standard first-line treatment for advanced clear cell renal cell cancer (ccRCC) yields promising outcomes, these regimens often lead to significant 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 significantly 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 benefit 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® technology-derived mRNA counts, and the clinical outcomes of 98 ccRCC patients treated with first-line antiangiogenics and determined its association with other genes implicated in ccRCC tumorigenesis.
Results: Higher AR-expression correlates significantly with better prognosis and survival based on the MSKCC risk score, and longer PFS. Furthermore, we have identified 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.
CITATION Clin Transl Oncol. 2024 Oct 4. doi: 10.1007/s12094-024-03652-9
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