Update on the Treatment of Metastatic Urothelial Carcinoma

Bukhari, Nedal; Al-Shamsi, Humaid O.; Azam, Faisal

doi:10.1155/2018/5682078

Cited by 38 publications

(33 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Historically, platinum‐based chemotherapy regimens have been the standard of care for UC and targeted therapies have not been used extensively in the course of clinical care . Trials of EGFR/ERBB2 TKIs in patients with UC who have tumours positive for RTK expression, but not for activating mutations or without any biomarker selection, have been largely unsuccessful .…”

Section: Discussionmentioning

confidence: 99%

Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions

Madison¹,

Gupta

Elamin

et al. 2020

BJU International

View full text Add to dashboard Cite

ObjectiveTo review the genomic landscape of advanced urothelial carcinoma (UC) to assess the frequencies of EGFR and ERBB2 (HER2) alterations. Materials and MethodsTumour specimens from 3753 patients with advanced UC were assayed with hybrid capture-based comprehensive genomic profiling of 180-395 genes. Tumour mutational burden (TMB) was assessed on 0.8 or 1.1 Mb of DNA, and is reported as mutations per megabase. ConclusionEGFR and ERBB2 alterations occur in 4% and 15% of UC, respectively. EGFR exon20ins and ERBB2 exon20ins were present in 0.7% and 0.5% of UC overall and collectively define a small, but distinct, subset of UC with infrequent co-occurrence of other drivers and low TMB. Given recent promising clinical studies of inhibitors with activity against exon 20 insertions in non-small cell lung cancer, consideration should be given to developing a trial inclusive of patients with UC harbouring these alterations.

show abstract

Section: Discussionmentioning

confidence: 99%

Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions

Madison¹,

Gupta

Elamin

et al. 2020

BJU International

View full text Add to dashboard Cite

show abstract

“…There is a large unmet medical need for exploring the mechanism of BCA metastasis and developing new treatments for BCA patients with progressive disease (Bukhari et al, 2018). In this study, we identified the loss of miR-3127 expression in BCA samples using qRT-PCR assays and the TCGA RNA-sequencing data of human BCA.…”

Section: Discussionmentioning

confidence: 99%

LINC00319-Mediated miR-3127 Repression Enhances Bladder Cancer Progression Through Upregulation of RAP2A

Wang

Meng

2020

Front. Genet.

View full text Add to dashboard Cite

Recent studies suggested that microRNA-3127 (miR-3127) was dysregulated in multiple tumor types and has important roles in tumorigenesis and cancer progression. However, its biological roles and the mechanisms that regulate its expression in bladder cancer (BCA) remain to be determined. The expression level of miR-3127 was measured in BCA tissues and its cellular functions were examined using both in vitro and in vivo experiments. The interaction between miR-3127 and long non-coding RNA (lncRNA) LINC00319 was explored using RNA immunoprecipitation assay and luciferase reporter assays. We showed that miR-3127 expression was significantly downregulated in human BCA tissues and BCA cell lines. Lower miR-3127 levels were associated with worse survival in BCA patients. The overexpression of miR-3127 impaired BCA cell proliferation and invasion, and the knockdown of miR-3127 enhanced BCA cell proliferation and invasion in vitro. Importantly, miR-3127 was able to suppress cell growth in vivo. We demonstrated that miR-3127 repressed the proliferation and invasion of BCA cells though directly targeted the 3-UTR of RAP2A, which served as a novel oncogene in BCA cells. The suppression of cell proliferation and invasion caused by miR-3127 overexpression could be partially abrogated by ectopic expression of RAP2A. Furthermore, high expression of LINC00319 was correlated with adverse survival in BCA patients. LINC00319 could bind directly with miR-3127 and inhibited its expression, and the tumor-promoting effects of LINC00319 could be reversed by re-expression of miR-3127 in BCA cells. Our findings indicated that lncRNA LINC00319-mediated miR-3127 repression promotes BCA progression through the upregulation of RAP2A. The re-introduction of miR-3127 or inhibition of LINC00319 might represent a promising therapeutic strategy for BCA treatment.

show abstract

“…Treatment at the non-muscle-invasive stage includes transurethral resection of bladder tumor often followed by intravesical chemotherapy or intravesical bacillus Calmette-Guérin immunotherapy [2]. Approximately 25% of patients with bladder cancer will be diagnosed with muscle-invasive disease [3]. Treatment of muscle-invasive bladder cancer includes surgery (cystectomy) combined with adjuvant or neo-adjuvant cisplatin-based chemotherapy [2], or synchronous chemoradiotherapy as an alternative to cystectomy [4], whereas patients with unresectable, locally advanced disease receive chemotherapy [5].…”

Section: Introductionmentioning

confidence: 99%

Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options

Koufopoulou¹,

Miranda

Kazmierska³

et al. 2020

Cancer Treatment Reviews

View full text Add to dashboard Cite

Background: Patients with advanced urothelial carcinoma (UC) have poor outcomes, with 5-year survival rates of < 5% for those with metastatic, stage IV disease. We have reviewed current treatment paradigms and emerging treatment options for these patients. Methods: The websites of seven national or international organizations were searched for metastatic UC treatment guidelines. Systematic literature reviews were conducted to identify evidence from randomized controlled trials (RCTs) of chemotherapy for patients with previously untreated, unresectable, stage IV UC. Searches included congress databases and articles published between 1990 and 2018. In order to align with the latest treatment paradigms in first-line advanced UC, a focused literature search was conducted to identify evidence supporting immuno-oncology (IO) agents. Results: For advanced UC, guidelines universally recommend cisplatin-based chemotherapy as first-line treatment for eligible patients and carboplatin-based regimens for those unfit to receive cisplatin. Despite the evaluation of a number of different cytotoxic regimens over the years, including triplet combinations, survival outcomes have not improved markedly with chemotherapy. Median overall survival with standard of care chemotherapy is ~13 months. Based on the results of single-arm, phase II studies, recent treatment guidelines have included atezolizumab (anti-PD-L1) and pembrolizumab (anti-PD-1) as first-line options for cisplatin-ineligible patients whose tumors express high levels of PD-L1. However, emerging evidence from RCTs of IO agents, including both cisplatin-eligible and cisplatin-ineligible patients, suggest that survival times exceeding 20 months are possible. Conclusions: After having reached a plateau with chemotherapy, the treatment landscape for advanced UC is evolving. Survival outcomes for patients with advanced UC are improving with treatment modalities involving IO agents.

show abstract

Update on the Treatment of Metastatic Urothelial Carcinoma

Cited by 38 publications

References 37 publications

Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions

Urothelial cancer harbours EGFR and HER2 amplifications and exon 20 insertions

LINC00319-Mediated miR-3127 Repression Enhances Bladder Cancer Progression Through Upregulation of RAP2A

Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options

Contact Info

Product

Resources

About