magnetic-resonance-imaging-assessment-carcinogen-induced-murine

Magnetic Resonance Imaging Assessment of Carcinogen-induced Murine Bladder Tumors

Murine bladder tumor models are critical for the evaluation of new therapeutic options. Bladder tumors induced with the N-butyl-N-(4-hydroxybutyl) ...

Northwestern University Feinberg School of Medicine

Stage T1 bladder cancers invade the lamina propria of the bladder and, despite sharing many of the genetic features of muscle-invasive bladder cancers, are classified as non-muscle-invasive or 'superficial' tumours. Yet, patients with T1 bladder cancer have an overall mortality of 33% and a cancer-specific mortality of 14% at three years after diagnosis, suggesting that these patients have a high risk of progression and, accordingly, require meticulous surgery, endoscopic surveillance and clinical decision-making. We hypothesize that the variability in the outcomes of patients with T1 bladder cancer is a result of both tumour heterogeneity and pathological staging, as well as inconsistencies in risk stratification, endoscopic resection and schedules of delivery of BCG. Owing to limitations in clinical staging, patients with T1 bladder cancer are at risk of both undertreatment with persistent use of BCG despite recurrence, and overtreatment with early cystectomy. Understanding the molecular features of T1 bladder cancers and how they respond to BCG therapy could improve biomarkers for risk stratification to align therapy with biological risk.

T1 bladder cancer: current considerations for diagnosis and management.

Bladder cancer is the fourth most common cancer in men and fifth most common overall. The use of next-generation sequencing (NGS) approaches is crucial to precisely characterize the molecular defects of tumors, and this information could be combined with other clinical data, such as tumor histology and TNM staging, with the goal of precise tumor classification. In many settings, targeted NGS is evaluated in patients with first- and second-line metastatic cancer. Yet, in the decade to come we anticipate increased application of precision oncology at all stages of bladder cancer with the aim of customizing cancer treatment. Here, we review the genomic and transcriptomic features associated with risk stratification in bladder cancer and summarize the current efforts for precision oncology in localized urothelial carcinomas.

Genomic classification and risk stratification of bladder cancer.

Bladder cancer is the fifth most common cancer in the United States and smoking is the largest known risk factor. Tobacco-derived carcinogens may induce the accumulation of somatic mutations in urothelial cells, and likely promote tumorigenesis. However, it is still unknown whether smoking-induced bladder carcinogenesis results in tumors with distinctive molecular features that can be therapeutically exploited.

Article	Year
T1 bladder cancer: current considerations for diagnosis and management. Nature reviews. Urology\| PubMed ID: 30323201	2019
Genomic classification and risk stratification of bladder cancer. World journal of urology\| PubMed ID: 30421072	2018
Molecular footprints of muscle-invasive bladder cancer in smoking and nonsmoking patients. Urologic oncology\| PubMed ID: 30446446	2018

Joshua J. Meeks

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