Molecular Research Efforts in Urothelial Carcinoma

Dear Colleagues,

Urothelial carcinoma of the bladder (UCB), as well as urothelial carcinoma of the upper urinary tract, represent one of the most interesting and emerging fields in terms of molecular oncology and uro-oncologic discovery efforts over recent years.

The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC) projects, and others are successful drivers in promoting genome sequencing efforts for the development of various genetic and molecular sub-classification systems in non-invasive, as well as muscle invasive UCB. Recently, several molecular subtypes of muscle-invasive UCB have been identified, of whom the basal subtype shared biomarkers with basal breast cancers and that were characterized by p63 activation, squamous differentiation, and aggressive disease at presentation [1]. Luminal muscle-invasive UCBs contained features of active PPARγ and estrogen receptor transcription, moreover they were enriched with activating FGFR3 mutations. p53-like UCBs were resistant to neoadjuvant MVAC-chemotherapy, adopting a p53-like phenotype after therapy. These findings have important implications for better prognostication, the future development of targeted agents, as well as disease management with chemotherapy.

Based on the progress in molecular oncology and cancer genetics in UCB, novel treatment options including immune-oncology drugs, FGFR inhibitors or other targeted agents are approved or under development. Research efforts should lead to the discovery of novel predictive biomarkers in this emerging field. In addition to alterations in transcriptome and proteome, epigenetic factors, DNA repair mechanisms and non-coding RNAs have been proposed as pathogenic drivers, tumor suppressors and factors in treatment resistance and patient’s clinical outcome.

Apart from the molecular viewpoint, the required treatment modalities (both surgical and medical), long-term follow-up of patients, as well enormous associated costs of UCB represent a tremendously growing and unsolved public health problem worldwide. Regarding the ten leading cancer types among males in the United States in 2018, estimated new UCB cases rank fourth, the associated estimated deaths rank at the eighth position, respectively [2].

Thus, an improved understanding of the underlying molecular mechanisms in UCB development is of paramount interest, not only to optimize treatment outcomes but to improve cost effective management modalities in this important malignancy. Original research articles, review articles, as well as research letters covering the large field of cancer genetics, molecular oncology, cell biology and newly discovered prognostic biomarkers of urothelial carcinoma are strongly invited.

References

1. Choi, W.; Porten, S.; Kim, S.; Willis, D.; Plimack, E.R.; Hoffman-Censits, J.; Roth, B.; Cheng, T.; Tran, M.; Lee, I.L.; et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell 2014, 25, 152–165.
2. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin. 2018, 68, 7–30.

Prof. Dr. Georg C. Hutterer
Guest Editor

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• Urothelial carcinoma of the bladder;
• Urothelial carcinoma of the upper urinary tract;
• Biomarkers;
• Targeted agents;
• Immune-oncology drugs;
• Epigenetic factors;
• DNA repair;
• Tumor suppressor factor