Item type: | Article | ||||
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Journal or Publication Title: | Annals of Oncology | ||||
Publisher: | Oxford Univ. Press | ||||
Place of Publication: | OXFORD | ||||
Volume: | 27 | ||||
Number of Issue or Book Chapter: | 7 | ||||
Page Range: | pp. 1311-1316 | ||||
Date: | 2016 | ||||
Institutions: | Medicine > Lehrstuhl für Urologie | ||||
Identification Number: |
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Keywords: | RADICAL CYSTECTOMY; UROTHELIAL CARCINOMA; CHEMOTHERAPY; EXPRESSION; TRIAL; GRADE; FGFR3; mutations; heterogeneity; bladder; cancer; targeted therapy | ||||
Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
Status: | Published | ||||
Refereed: | Yes, this version has been refereed | ||||
Created at the University of Regensburg: | Yes | ||||
Item ID: | 42644 |
Abstract
Fibroblast growth factor receptor 3 (FGFR3) is a major potential actionable target in urothelial bladder cancer (BC). We found that FGFR3 mutations appeared conserved in primary BC and corresponding lymph-node metastases. We also showed that the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. This suggests that personalized anti-FGFR3 therapy may ...
Abstract
Fibroblast growth factor receptor 3 (FGFR3) is a major potential actionable target in urothelial bladder cancer (BC). We found that FGFR3 mutations appeared conserved in primary BC and corresponding lymph-node metastases. We also showed that the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. This suggests that personalized anti-FGFR3 therapy may improve BC treatment in the perioperative setting.Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated >FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. We evaluated possible >FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, >n = 61) and in radical cystectomy (RC, >n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, >n = 201). We found ZFGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) a parts per thousand yenT2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight >FGFR3 mutant a parts per thousand yenT2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) >FGFR3 mutations in RC specimens. >FGFR3 mutation was associated with pN0 (>P < 0.001) at RC. In 10/201 (5%) LN+, an >FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. >FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.
Metadata last modified: 03 Mar 2021 10:19