التفاصيل البيبلوغرافية
| العنوان: |
Genomic Landscape of Vinflunine Response in Metastatic Urothelial Cancer. |
| المؤلفون: |
Bernardini, Alejandra, Dueñas, Marta, Martín-Soberon, María Cruz, Rubio, Carolina, Suarez-Cabrera, Cristian, Ruiz-Palomares, Raquel, Munera-Maravilla, Ester, Lázaro, Sara, Lodewijk, Iris, Rueda, Daniel, Gómez-Sánchez, David, Alonso-Gordoa, Teresa, Puente, Javier, Pinto, Álvaro, González-Peramato, Pilar, Aguado, Carlos, Herrera, Mercedes, López, Flora, Martinez, Victor M. G., Morales, Lucía |
| المصدر: |
Cancers; Feb2022, Vol. 14 Issue 2, p378-378, 1p |
| مصطلحات موضوعية: |
CANCER chemotherapy, THERAPEUTIC use of antineoplastic agents, SEQUENCE analysis, FORMALDEHYDE, METASTASIS, ANTINEOPLASTIC agents, URINARY organs, COMPARATIVE studies, GENE expression, GENOMICS, HISTOLOGICAL techniques, UNIVERSITIES & colleges, DESCRIPTIVE statistics, TUMOR markers, COLLECTION & preservation of biological specimens, PHARMACODYNAMICS |
| مصطلحات جغرافية: |
SPAIN |
| مستخلص: |
Simple Summary: Few metastatic urothelial cancer patients achieve durable clinical benefit with vinflunine. Predictive biomarkers to help to identify better treatment strategies are extremely needed. The objective of this study was to identify molecular differences between extreme responders to vinflunine in urothelial cancer. Genomic and immune markers are potentially useful identifying patients that may achieve greater benefit with vinflunine. Background and Aims: Metastatic urothelial carcinoma (mUC) remains an incurable disease with limited treatment options after platinum-based chemotherapy and immune checkpoint blockade (ICB). Vinflunine has shown a modest increase in overall survival and remains a therapeutic option for chemo- and immunotherapy refractory tumours. However, biomarkers that could identify responding patients to vinflunine and possible alternative therapies after failure to treatment are still missing. In this study, we aimed to identify potential genomic biomarkers of vinflunine response in mUC patient samples and potential management alternatives. Methods: Formalin-fixed paraffin-embedded samples of mUC patients (n = 23) from three university hospitals in Spain were used for genomic targeted-sequencing and transcriptome (using the Immune Profile panel by NanoString) analyses. Patients who received vinflunine after platinum-based chemotherapy failure were classified in non-responders (NR: progressive disease ≤ 3 months; n= 11) or responders (R: response ≥ 6 months; n = 12). Results: Genomic characterization revealed that the most common alteration, TP53 mutations, had comparable frequency in R (6/12; 50%) and NR (4/11; 36%). Non-synonymous mutations in KTM2C (4/12; 33.3%), PIK3CA (3/12; 25%) and ARID2 (3/12; 25%) were predominantly associated with response. No significant difference was observed in tumour mutational burden (TMB) between R and NR patients. The NR tumours showed increased expression of diverse immune-related genes and pathways, including various interferon gamma-related genes. We also identified increased MAGEA4 expression as a potential biomarker of non-responding tumours to vinflunine treatment. Conclusions: Our data may help to identify potential genomic biomarkers of response to vinflunine. Moreover, tumours refractory to vinflunine showed immune signatures potentially associated with response to ICB. Extensive validation studies, including longitudinal series, are needed to corroborate these findings. [ABSTRACT FROM AUTHOR] |
|
Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder