Critical Overview of HER2 Assessement in Bladder Cancer: What Is Missing for a Better Therapeutic Approach?

Cîmpean, Anca Maria; Tarlui, Valeria; Cumpanas, A.; Bolintineanu, Sorin; Cumpanas, Andrei Dragos; Raica, Marius

doi:10.21873/anticanres.11903

Cited by 5 publications

(4 citation statements)

References 39 publications

(42 reference statements)

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“…Finally, in the meta-analysis literature we included, HER2 expression was measured by the IHC method only. It has been suggested that the results of IHC and fluorescence in situ hybridization (FISH) were not completely consistent when detecting HER2 expression in bladder cancer (52,53). A combination of FISH assays is needed for further research in the future.…”

Section: Discussionmentioning

confidence: 99%

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis

et al. 2021

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ObjectiveHuman Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in multiple malignancies and associated with patients’ prognosis, but its role in bladder cancer (BCa) remains elusive. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in BCa.MethodsPubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and BCa pathological features. TCGA was mined for the information regarding as well.ResultsOur study included 14 articles enrolling 1398 people. Expression of HER2 is higher in bladder cancer than in normal tissues. HER2 over-expression is associated with CIS, multifocal tumor, large tumor size, high tumor stage and grade, lymph node metastasis, progression, recurrence and papillary tumor. We could not find a significant association between HER2 expression and survival time in BCa patients.ConclusionsOur meta and bioinformatic analysis indicated that HER2 expression was related to pathological malignancy and poor prognosis in BCa.

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Section: Discussionmentioning

confidence: 99%

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis

et al. 2021

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“…In considering a different molecular target, HER-2 (EGFR2/ERBB2/NEU) has been found to be significantly overexpressed in canine InvUC samples when compared to non-neoplastic urothelium (79), as is the case in human InvUC (80,81). In two immunohistochemical studies HER-2 immunoreactivity was noted in 13 of 23 (56%) and in 14 of 23 (60.9%) cases of canine InvUC, respectively (79, 82).…”

Section: Other Molecular Featuresmentioning

confidence: 99%

Naturally-Occurring Invasive Urothelial Carcinoma in Dogs, a Unique Model to Drive Advances in Managing Muscle Invasive Bladder Cancer in Humans

et al. 2020

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There is a great need to improve the outlook for people facing urinary bladder cancer, especially for patients with invasive urothelial carcinoma (InvUC) which is lethal in 50% of cases. Improved outcomes for patients with InvUC could come from advances on several fronts including emerging immunotherapies, targeted therapies, and new drug combinations; selection of patients most likely to respond to a given treatment based on molecular subtypes, immune signatures, and other characteristics; and prevention, early detection, and early intervention. Progress on all of these fronts will require clinically relevant animal models for translational research. The animal model(s) should possess key features that drive success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). Experimental animal models, while essential in bladder cancer research, do not possess these collective features to accurately predict outcomes in humans. These key features, however, are present in naturally-occurring InvUC in pet dogs. Canine InvUC closely mimics muscle-invasive bladder cancer in humans in cellular and molecular features, molecular subtypes, immune response patterns, biological behavior (sites and frequency of metastasis), and response to therapy. Thus, dogs can offer a highly relevant animal model to complement other models in research for new therapies for bladder cancer. Clinical treatment trials in pet dogs with InvUC are considered a win-win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. In addition, the high breedassociated risk for InvUC in dogs (e.g., 20-fold increased risk in Scottish Terriers) Knapp et al. Canine Bladder Cancer-Translational Model offers an unparalleled opportunity to test new strategies in primary prevention, early detection, and early intervention. This review will provide an overview of canine InvUC, summarize the similarities (and differences) between canine and human InvUC, and provide evidence for the expanding value of this canine model in bladder cancer research.

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“…Cox-2 is also overexpressed in more than 80% of human (Bourn et al 2019) and canine BC (Knapp et al 2014). HER-2 (EGFR2/ERBB2/NEU) has been found to be signi cantly overexpressed in canine invasive BC (Millanta et al 2018), as is the case in human invasive BC (Eriksson et al 2017;Cimpean et al 2017) when compared to non-neoplastic urothelium. The standard treatment options for invasive BC in humans and dogs are nearly similar and both species showed similar responses to treatments (Knapp et al 2019).…”

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confidence: 89%

Experimental Methods for Establishing and Maintaining Canine Bladder Cancer Organoids

Elbadawy,

Zdyrski,

Wickham

et al. 2024

Preprint

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Dogs share many anatomical and physiological characteristics with humans and, in certain instances, represent a more reliable research model than rodents for some diseases, including several types of human cancer. Advances in adult stem cell research have accelerated the development of 3D organoid cultures in non-model animals, such as dogs. These advancements have the potential to significantly impact disease modeling, biomarker discovery, and drug development for both human and canine diseases, including bladder cancer (BC). In this Chapter, we present a standardized protocol for generating BC organoids from canines. The chapter describes the detailed methodology for establishing canine BC organoids from urine or tissue-derived stem cells. Additionally, it highlights the potential of these organoids to recapitulate the expression of key markers from their original tissues and their utility in various biomedical applications such as drug screening, gene mutation analysis, and toxicology. Finally, we discuss potential future research directions for canine BC organoids in translational research.

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Critical Overview of HER2 Assessement in Bladder Cancer: What Is Missing for a Better Therapeutic Approach?

Abstract: Improved HER2 assessement is needed for urothelial carcinomas. HER2-IHC scored as 0-2 should be validated by and reclassified according to FISH analysis.

Cited by 5 publications

References 39 publications

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis

The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: A Meta-Analysis and a Bioinformatic Analysis

Naturally-Occurring Invasive Urothelial Carcinoma in Dogs, a Unique Model to Drive Advances in Managing Muscle Invasive Bladder Cancer in Humans

Experimental Methods for Establishing and Maintaining Canine Bladder Cancer Organoids

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