Genetic and Epigenetic Alterations in Bladder Cancer

Abstract

Bladder cancer is one of the most common cancers worldwide, with a high rate of recurrence and poor outcomes as a result of relapse. Bladder cancer patients require lifelong invasive monitoring and treatment, making bladder cancer one of the most expensive malignancies. Lines of evidence increasingly point to distinct genetic and epigenetic alteration patterns in bladder cancer, even between the different stages and grades of disease. In addition, genetic and epigenetic alterations have been demonstrated to play important roles during bladder tumorigenesis. This review will focus on bladder cancer-associated genomic and epigenomic alterations, which are common in bladder cancer and provide potential diagnostic markers and therapeutic targets for bladder cancer treatment.

Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF‐κB‐modulated tumor progression in bladder cancer in vitro and in vivo

“…Impact of genetic alterations on dysregulated signaling transduction has been found in muscle invasive bladder cancers (MIBCs) and non‐MIBCs (NMIBCs) . The p53 and RB (retinoblastoma) tumor suppressor pathway which controls restriction of cell cycle progression is altered and negatively regulated by mutation of tumor suppressor genes and expression of oncogenes . Hyperactivation of Ras/mitogen‐activated protein kinase (MAPK) pathway contributes to tumor progression.…”

“…5 The p53 and RB (retinoblastoma) tumor suppressor pathway which controls restriction of cell cycle progression is altered and negatively regulated by mutation of tumor suppressor genes and expression of oncogenes. 6 Hyperactivation of Ras/mitogenactivated protein kinase (MAPK) pathway contributes to tumor progression. Overexpression of Ras/MAPK pathway is modulated by Ras, HER2 and HER3 mutation, and EGFR amplification in bladder cancer.…”

“…Ras/MAPK pathway has been targeted by tyrosine kinase inhibitors (TKIs) in clinical trials. 4,[6][7][8] Regorafenib (Stivarga) is an oral multiple kinase inhibitor which targets several critical signaling molecules including angiogenic, stromal, oncogenic receptor tyrosine kinases and already approved for treatment of patients with colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma (HCC). 9,10 Regorafenib has been indicated to diminish tumor progression through suppression of MAP-K/extracellular signal-regulated kinase (ERK) activation in HCC in vitro and in vivo 11,12 .…”

lncRNA TUC338 is a potential diagnostic biomarker for bladder cancer

“…5 Genetic and epigenetic alterations are the main players in the development of bladder cancer. 6 However, the limited number of tumor suppressor and oncogenes identified so far may be not sufficient to explain the complicated molecular pathogenesis of this disease. 7 Although long noncoding RNAs (>200 nucleotides, lncRNAs) lack the ability of protein coding, they participate in both normal biological processes and the development of human disease by regulating gene expression.…”

Are We Ready to Use the Omics Strategies for Precision Medicine?

“…His discussion delves into how we can develop novel methods of characterizing epigenetic changes and how to monitor these changes in patients. His article [3] includes detailed information on current research, ranging from somatic genetic aberrations to various epigenetic regulations such as DNA methylation, histone modifications, microRNA regulation, and nucleosome positioning. He also provides evidence suggesting genetic and epigenetic alterations as possible therapeutic targets.…”