Health / Medical Topics |
Bladder Cancer Pathway
Bladder cancers arise and progress along two distinctive pathways. The first of these is often preceded by simple and papillary hyperplasia and exhibits a tumour morphology that is low-grade, superficial and papillary. Papillary carcinoma has a tendency to recur locally, but rarely invades and metastasizes. These tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. The second tumour pathway is characterized by high-grade muscle-invasive tumours, which either originate from flat carcinoma in situ (CIS)/severe dysplasia or arise de novo. Over half of these tumours show defects in the tumour suppressors p53 and/or the retinoblastoma protein (RB) genes and pathways, and over 50% of these tumours progress to local and distant metastases. Some of the cell cycle-related molecules show evidence of epigenetic modulation through aberrant promoter hypermethylation in invasive bladder cancer. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF). (NCI Thesaurus/KEGG)