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A review of molecular predictors of response to chemotherapy in urothelial carcinoma of the bladder

Lookup NU author(s): Dr Zafer Tandogdu


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© 2016 Bentham Science Publishers. Locally advanced and metastatic urothelial carcinomas of the bladder (UCB) are associated with decreased survival. Currently the two main definitive treatment options for invasive bladder cancer are radiotherapy or surgery (radical cystectomy), typically with neo-adjuvant chemotherapy for both options. Radical cystectomy (RC) with urinary diversion is to date the gold standard of surgical treatment. Neoadjuvant chemotherapy (NAC) prior to RC might be associated with survival advantage compared to RC alone. However, its usefulness has been called into question due to concerns of overtreatment and toxicity. Thus, prediction of the individual harms and benefits gained from NAC would be an important step individualized medicine. In this context we have reviewed the current published literature to identify the role of molecular markers. Furthermore, we outline how recent developments in whole-genome sequencing may improve the selection of targeted cancer drugs and facilitate individualized treatment. It has been shown that altered expression of markers of cell-cycle regulation, such as p21, p53, and pRb, are associated with poor oncological outcome in patients undergoing radical cystectomy for bladder cancer. On the other hand members of the Bcl-2 and heat-shock protein 60 (HSP60) families were found to be associated with better survival in patients undergoing cisplatin-based NAC. Conversely, overexpression of vascular endothelial growth factor (VEGF) or fibroblast growth factor receptor 3 (FGFR3) has been associated with resistance to cisplatin-based NAC and adverse outcomes. The excision repair cross complementing 1 (ERCC1) protein failed to predict response to cisplatin-based NAC. Recent advances in whole-genome sequencing can identify new molecular targets in most of UCB tumors.

Publication metadata

Author(s): Degener S, Mata DA, Youssef R, Godde D, Tandogdu Z, Roth S, Von Rundstedt F-C

Publication type: Review

Publication status: Published

Journal: Mini-Reviews in Medicinal Chemistry

Year: 2018

Volume: 18

Issue: 13

Pages: 1133-1142

Online publication date: 31/07/2018

Acceptance date: 02/04/2016

ISSN (print): 1389-5575

ISSN (electronic): 1875-5607

Publisher: Bentham Science Publishers B.V.


DOI: 10.2174/1389557516666160315114522