scholarly journals Research on new drugs in the therapy of bladder cancer (BC)

2018 ◽  
Vol 72 ◽  
pp. 442-448 ◽  
Author(s):  
Karolina Jurkowska ◽  
Anna Długosz

New, more effective and safer therapies in bladder cancer are being developed. Most attention is focused on monoclonal antibody therapies, targeted therapies and immunotherapy. Numerous pre-clinical and clinical studies on the use of the new drugs in bladder cancer are currently in progress. The great hope is associated with monoclonal antibodies, which are immune checkpoint inhibitors. Last year, two drugs from this group (Atezolizumab and Nivolumab) have been approved by Food and Drug Administration (FDA) for the treatment of muscle invasive bladder cancer (MIBC). Other monoclonal antibodies in this group such as Pembrolizumab are also in clinical trials. Much attention is also focused on targeted therapies. Inhibitors of: VEGF (vascular endothelial growth factor), EGFR (epidermal growth factor receptor), HER-2 (human epidermal growth factor receptor 2) and mTOR kinase are examined in bladder cancer. These drugs are often studied as a combination therapy with chemioterapeutic agents. Alternatives for BCG (Bacillus Calmette-Guérin) therapy in non muscle invasive bladder cancer (NMIBC) are also being developed. Research on the use of new vaccines and other immunotherapies (e.g. IL-12 therapy) are underway. The aim of this paper is to present the direction of current trends in bladder cancer treatment and what changes in therapy we can expect in the future. The drugs in clinical trials and those already registered in other countries have been reviewed. The latest drug-based therapeutic solutions have been described, which can replace traditional chemotherapy in the future.

2019 ◽  
Vol 8 (11) ◽  
pp. 1954
Author(s):  
Yun Chiang ◽  
Chung-Chieh Wang ◽  
Yu-Chieh Tsai ◽  
Chao-Yuan Huang ◽  
Yeong-Shiau Pu ◽  
...  

The aim of this study was to investigate prognostic molecular targets for selecting patients with muscle-invasive bladder cancer undergoing bladder-preserving therapy. Pretreatment biopsy samples from patients with muscle-invasive bladder cancer receiving trimodality bladder-preserving therapy were analyzed for expression levels of p53, p16, human epidermal growth factor receptor-2 (Her-2), epidermal growth factor receptor (EGFR), nuclear factor-kappa B (NFκB; p65), E-cadherin, matrix metalloproteinase-9 (MMP9), meiotic recombination 11 homolog (MRE11), programmed death-1 ligand (PD-L1), and mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemical (IHC) staining. The correlations between these molecular markers with local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and overall survival (OS) were explored. Biopsy samples from 41 out of 60 patients were evaluated using IHC. Univariate analysis revealed that the high expression of NFκB is associated with significantly worse LPFS, DMFS, and OS, and low expression of p16 is associated with significantly lower LPFS. Upon further multivariate analysis including sex, age, stage, and selected unfavorable factors in the model, NFκB and p16 independently remained significant. The investigational in vitro study demonstrated that irradiation induces up-regulation of NFκB signaling. Irradiated bladder cancer cells showed increased invasion capability and clonogenic survival; inhibition of NFκB signaling by an NFκB inhibitor, SC75741, or RNA interference reversed the observed increases. NFκB expression (p65) is associated with prognostic significance for both LPFS and DMFS in patients treated with bladder-preserving therapy, with consistent impact on cell viability of bladder cancer cells. NFκB may be a putative molecular target to help with outcome stratification.


Sign in / Sign up

Export Citation Format

Share Document