Precision Oncology Approach for Urachal Carcinoma: A Clinical Case Report.

Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients.

Clofarabine Has a Superior Therapeutic Window as compared to Gemcitabine in Preclinical Bladder Cancer Models.

Current standard-of-care systemic therapy options for locally advanced and metastatic bladder cancer (BC), which are predominantly based on cisplatin-gemcitabine combinations, are limited by significant treatment failure rates and frailty-based patient ineligibility. We previously addressed the urgent clinical need for better-tolerated BC therapeutic strategies using a drug screening approach, which identified outstanding antineoplastic activity of clofarabine in preclinical models of BC. To further assess clofarabine as a potential BC therapy component, we conducted head-to-head comparisons of responses to clofarabine versus gemcitabine in preclinical in vitro and in vivo models of BC, complemented by in silico analyses.

Preclinical models for bladder cancer therapy research.

Purpose Of Review: Bladder cancer (BC) is a highly heterogenous disease comprising tumours of various molecular subtypes and histologic variants. This heterogeneity represents a major challenge for the development of novel therapeutics. Preclinical models that closely mimic in vivo tumours and reflect their diverse biology are indispensable for the identification of therapies with specific activity in various BC subtypes.

Evaluation of APOBEC3 expression as prognostic marker in squamous cell carcinoma of the penis.

Squamous cell carcinoma of the penis (PSC) is a rare disease with limited information on the molecular events leading to malignant transformation. In a third of PSC cases, presence of human papilloma virus (HPV) is found. The APOBEC3 family of proteins is known to play a significant role in defense against HPV infection, but their role in PSC is largely unknown.

Molecular and Pharmacological Bladder Cancer Therapy Screening: Discovery of Clofarabine as a Highly Active Compound.

Background: The heterogeneity of bladder cancers (BCs) is a major challenge for the development of novel therapies. However, given the high rates of recurrence and/or treatment failure, the identification of effective therapeutic strategies is an urgent clinical need.

Objective: We aimed to establish a model system for drug identification/repurposing in order to identify novel therapies for the treatment of BC.

Discovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer.

Background: Bacillus Calmette-Guérin (BCG) immunotherapy, the standard adjuvant intravesical therapy for some intermediate and most high-risk non-muscle invasive bladder cancers (NMIBCs), suffers from a heterogenous response rate. Molecular markers to help guide responses are scarce and currently not used in the clinical setting.

Methods: To identify novel biomarkers and pathways involved in response to BCG immunotherapy, we performed a genome-wide DNA methylation analysis of NMIBCs before BCG therapy.

Aristolochic acid and its effect on different cancers in uro-oncology.

Purpose Of Review: To acquaint urologists with aristolochic acid nephropathy, an iatrogenic disease that poses a distinct threat to global public health. In China alone, 100 million people may currently be at risk. We illustrate the power of molecular epidemiology in establishing the cause of this disease.

Fibroblast growth factor receptors across urothelial carcinoma landscape.

Purpose Of Review: Fibroblast growth factor receptor (FGFR) signalling, especially induced by FGFR3, is a crucial factor in the pathogenesis of urothelial carcinoma and was therefore extensively studied over the last decades. In this review, we summarize the most relevant findings of the past two years.

Recent Findings: Recent studies support the concept that FGFR3 mediates a pathway of urothelial carcinogenesis associated with low malignant potential.

Epigenetic alterations of testicular germ cell tumours.

Purpose Of Review: Testicular germ cell tumours (TGCTs) exhibit, in contrast to other cancer types, a relatively low mutational burden. However, numerous epigenetic alterations have been shown to impact TGCT. In this review, we summarize the most relevant findings of the past 2 years.

Progressive tissue biomarker profiling in non-muscle-invasive bladder cancer.

The recurrence rate of non-muscle-invasive bladder cancer (NMIBC) is up to 60% within the first year of therapy. Accurate risk stratification is necessary for patient counselling, follow-up scheduling and individualized therapeutic decision making. Current prognostic models rely on clinicopathologic features, but their discrimination remains limited when in external cohorts.

Waiting in the wings: the emerging role of molecular biomarkers in bladder cancer.

Bladder cancer (BCa) is the fifth most frequently diagnosed cancer worldwide and is, in fact, the most expensive cancer on a per-patient to treat basis. There is a critical need to implement new tests into clinical practice to improve the quality of clinical care, decrease unnecessary invasive therapies and ultimately save costs. Currently, no molecular or genetic biomarker has been widely integrated into daily clinical practice.

RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1.

Notch signaling is an evolutionarily conserved signal transduction pathway that is essential for metazoan development. Upon ligand binding, the Notch intracellular domain (NOTCH ICD) translocates into the nucleus and forms a complex with the transcription factor RBPJ (also known as CBF1 or CSL) to activate expression of Notch target genes. In the absence of a Notch signal, RBPJ acts as a transcriptional repressor.

Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits During Caenorhabditis elegans Development.

SWI/SNF ATP-dependent chromatin-remodeling complexes have been related to several cellular processes such as transcription, regulation of chromosomal stability, and DNA repair. The Caenorhabditis elegans gene ham-3 (also known as swsn-2.1) and its paralog swsn-2.

Cytoplasmic LSM-1 protein regulates stress responses through the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.

Genes coding for members of the Sm-like (LSm) protein family are conserved through evolution from prokaryotes to humans. These proteins have been described as forming homo- or heterocomplexes implicated in a broad range of RNA-related functions. To date, the nuclear LSm2-8 and the cytoplasmic LSm1-7 heteroheptamers are the best characterized complexes in eukaryotes.