scholarly journals CCDC6 and USP7 expression levels suggest novel treatment options in high-grade urothelial bladder cancer

Author(s):  
Francesco Morra ◽  
Francesco Merolla ◽  
Daniela Criscuolo ◽  
Luigi Insabato ◽  
Riccardo Giannella ◽  
...  
2021 ◽  
Author(s):  
Shouhua Pan ◽  
Si Li ◽  
Mingzhe Xiao ◽  
Dongsheng Chen ◽  
Junlong Li

Abstract Urothelial bladder cancer (UBC) is a common malignancy with significant mortality worldwide. However, treatment options of UBC were mainly chemotherapy and immunotherapy since few targeted agents had shown efficacy in UBC. In recent studies, everolimus has showed antitumor activity in patients harboring aberrations in PI3K/Akt/mTOR pathway in multiple tumor types. Here we report a patient with metastatic UBC harboring a rare M1043I mutation of PIK3CA detected by DNA based next-generation sequencing. The patient received everolimus as first-line therapy after palliative transurethral resection. Within one months, the residual lymph node metastases achieved complete response and no more ostealgia was reported. To our knowledge, this is the first case reporting a significant benefit from everolimus in PIK3CA mutant UBC, suggesting the rare M1043I mutation variant may be a potential biomarker of sensitivity to everolimus. Further mechanism insights and clinical studies are needed to clarify the effectiveness of everolimus in patients with PIK3CA M1043I mutation.


2021 ◽  
Vol 93 (2) ◽  
pp. 143-147
Author(s):  
Lampros Mitrakas ◽  
Stavros Gravas ◽  
Foteini Karasavvidou ◽  
Ioannis Zachos ◽  
Anastasios Karatzas ◽  
...  

Objective: To conduct a prospective study of the potential prognostic role of endothelin-1 (ET-1) in a cohort of primary high-grade non-muscle-invasive urothelial bladder cancer patients, who were treated with adjuvant intravesical Bacillus Calmette-Guérin (BCG). Material and methods: Patients with primary high-grade nonmuscle- invasive urothelial bladder cancer, who received postoperatively induction and maintenance BCG therapy, were prospectively included. Recurrence and progression were histologically proven. Immunohistochemical staining for ET-1 was assessed. Epidemiological, pathological and clinical parameters as well as the expression of ET-1 in tumor specimens were statistically analyzed for recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS). Results: ET-1 associates significantly with recurrence (p = 0.000), progression (p = 0.000), RFS (p = 0.000) and PFS (p = 0.000). The patient’s age is also significant for recurrence (p = 0.003, OR = 1.273 95% CI: 1.086-1.492) and RFS (p = 0.013). Conclusions: ET-1 seems to deteriorate prognosis in patients suffering from primary high-grade non-muscle-invasive urothelial bladder cancer, who are treated with adjuvant BCG instillations. Furthermore, the patient’s age associates with an increased likelihood for recurrence.


2020 ◽  
Vol 43 (5) ◽  
pp. 807-819 ◽  
Author(s):  
Tician Schnitzler ◽  
Nadina Ortiz-Brüchle ◽  
Ursula Schneider ◽  
Isabella Lurje ◽  
Karolina Guricova ◽  
...  

Abstract Purpose Non-invasive high-grade (HG) bladder cancer is a heterogeneous disease that is characterized insufficiently. First-line Bacillus Calmette-Guérin instillation fails in a substantial amount of cases and alternative bladder-preserving treatments are limited, underlining the need to promote a further molecular understanding of non-invasive HG lesions. Here, we characterized pure HG papillary urothelial bladder cancer (pure pTa HG), a potential subgroup of non-invasive HG bladder carcinomas, with regard to molecular subtype affiliation and potential for targeted therapy. Methods An immunohistochemistry panel comprising luminal (KRT20, ERBB2, ESR2, GATA3) and basal (KRT5/6, KRT14) markers as well as p53 and FGFR3 was used to analyze molecular subtype affiliations of 78 pure pTa HG/papillary pT1(a) HG samples. In 66 of these, ERBB2 fluorescence in situ hybridization was performed. Additionally, targeted sequencing (31 genes) of 19 pTa HG cases was conducted, focusing on known therapeutic targets or those described to predict response to targeted therapies noted in registered clinical trials or that are already approved. Results We found that pure pTa HG/papillary pT1(a) HG lesions were characterized by a luminal-like phenotype associated with frequent (58% of samples) moderate to high ERBB2 protein expression, rare FGFR3 alterations on genomic and protein levels, and a high frequency (89% of samples) of chromatin-modifying gene alterations. Of note, 95% of pTa HG/papillary pT1 HG cases harbored at least one potential druggable genomic alteration. Conclusions Our data should help guiding the selection of targeted therapies for investigation in future clinical trials and, additionally, may provide a basis for prospective mechanistic studies of pTa HG pathogenesis.


2016 ◽  
Vol 160 (4) ◽  
pp. 578-582 ◽  
Author(s):  
Milan Kral ◽  
Jaroslav Michalek ◽  
Jozef Skarda ◽  
Tomas Tichy ◽  
Oldrich Smakal ◽  
...  

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