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Systemic therapy is the mainstay of treatment for metastatic urothelial carcinoma (UC). Responses to first-line platinum-based therapy tend to be short-lived with potential toxicity. Despite the approval of checkpoint inhibitors, the long-term prognosis for patients with metastatic UC remains dismal. Herein we report the case of a patient with a solitary pulmonary metastatic lesion of urothelial origin as the only site of metastatic disease who remained free of disease for more than 2 years without systemic therapy after metastasectomy. We review the literature discussing the role of combined surgical and medical management of oligometastatic UC. As our case illustrates, a growing body of evidence suggests a potential role for a multimodal approach in patients with oligometastatic UC.

In a cohort of 104 patients with metastatic urothelial carcinoma (mUC) who had received platinum therapy, we examined the correlation between ERCC1, RAD51, PARP-1, PAR, BRCA1, and BRCA2 and overall survival (OS). A greater percentage of nuclear staining of ERCC1 (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P = .0007), RAD51 (HR, 5.6; 95% CI, 1.7-18.3; P = .005), and PAR (HR, 2.2; 95% CI, 1.1-4.4; P = .026) was associated with worse OS.

Despite a detailed understanding of the molecular aberrations driving the development of urothelial cancers, this knowledge has not translated into advances for the treatment of this disease. Urothelial cancers are chemosensitive and platinum-based combination chemotherapy remains the standard of care for advanced disease, as well as neoadjuvant and adjuvant therapy for locally advanced disease. However, nearly half of patients who undergo resection of locally advanced urothelial cancer will relapse and eventually develop platinum-resistant disease. Clinical trials of targeted agents against angiogenesis and growth factors, as well as novel chemotherapeutics, have generally been unsuccessful in urothelial cancers. Improvements in the therapeutic arsenal for urothelial cancer depend upon identification of new targets and strategies to overcome platinum resistance.

Ovarian cancer is the leading cause of gynecologic cancer death in the Western world and more than 70% of patients are diagnosed with advanced stage disease. The high mortality rate is due to the difficulty in the early detection of ovarian cancer. Current screening strategies lack the necessary sensitivity and specificity to reliably and accurately diagnose affected women, prompting investigators to seek alternative means of analysis found in protein pathways and networks. Proteomics seeks to advance the understanding of how proteins interact in cancer and may provide a mechanism for early stage diagnosis. The proteomic techniques of laser capture microdissection, mass spectrometry and tissue lysate arrays have led to the discovery of new biomarkers and the identification, development and approval of a number of targeted therapeutic agents. Following validation through clinical trials, the application of these techniques will contribute to the changing paradigm of cancer detection and treatment toward personalized medicine.

ABSTRACTTo better understand the mechanisms responsible for the observed effects of deletions in the promoter region of the latency-associated transcript (LAT) gene in impairing herpes simplex virus (HSV) reactivation, we generated mice transgenic for a 5.5-kb HSV type 2 (HSV-2) genomic fragment spanning the major LAT, along with the LAT promoter and flanking regions, in the C57BL/6 background. The mice expressed abundant 2.2-kb major LATs in trigeminal ganglia (TG) and other tissues. The effects of the transgene on HSV-2 infection, latency, and reactivation were assessed. When infected with wild-type (WT) HSV-2 or its LAT promoter deletion (LAT-) mutant, primary lung fibroblast lines established from normal C57BL/6 and transgenic mice supported virus growth equally well. The replication of these viruses in the mouse eye and their spread to TG and brains were similar. The quantities of latent viral DNA in TG of transgenic and normal mice, as determined by real-time PCR, were comparable. UV light-induced reactivation of the LAT-mutant from transgenic mice (0 to 7%) was no more frequent than that from normal mice (0 to 14%), while WT virus was reactivated from 13 to 54% of normal mice and 22 to 54% of transgenic mice. The cumulative data indicate that, when expressed transgenically, the HSV-2 major LAT cannot influence HSV-2 infection or latency and cannot complement the defect in reactivation of the LAT-mutant. These results imply that the phenotype of reduced reactivation associated with the LAT-mutant is related to a function encoded in the LAT promoter but not to the major LAT itself.

Off Label Use: Rituximab is an anti-CD20 chimeric antibody and is used for the treatment of immune thrombocytopenic purpura.

Abstract 4996