Bladder Cancer Biology

Abstract

At present, bladder cancer (BCa) is worldwide the 9 th most common tumor; in men it represents the 7 th and in women 17 th most common malignancy (Ploeg et al., 2009). In the European Union approximately 104,400 newly diagnosed BCa and 36,500 BCa-related deaths were estimated for the year 2006 (Ferlay et al., 2007). In the United States, approximately 70,530 new cases and 14,680 BCa-related deaths were expected for 2010 (Jemal et al., 2010). Men are three to four times more frequently affected than women (Ferlay et al., 2007; Jemal et al., 2010). Detection of BCa is hampered due to lately emerging symptoms, such as hematuria, and the lack of specific tumor markers. Treatment options, particularly for the advanced disease, appear currently insufficient, leading together with the BCa-inherent high recurrence and progression rates to the relatively high BCa-related mortality (Ferlay et al., 2007). For the development of more specific and efficient diagnostic tools and therapeutic approaches a profound understanding of the onset and course of this disease is indispensable. Molecular alterations that presumably lead to malignant transformation of the bladder urothelium belong to specified pathways involved in regulation of cellular homeostasis. As consequence of genetic and epigenetic alterations as well as of changes in subsequent regulatory mechanisms several major cellular processes are influenced in a manner that results in tumor development and progression. Regulation of the cell cycle, cell death and cell growth belong to these processes as well as the control of signal transduction and gene regulation. Particularly important for tumor cell spread and metastasis are changes in the regulation of interactions with stromal cells and extracellular components, of tumor cell migration and invasion and of angiogenesis (Mitra & Cote, 2009). Interestingly, numerous associations between risk factors for the development of BCa and the affected cellular processes were identified (Mitra & Cote, 2009). For tobacco smoking or the occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons and aniline dyes − the major environmental risk factors that contribute to BCa genesis − strong associations with alterations in cell cycle regulation have been reported (