Abstract
Muscle-invasive urothelial carcinoma (MIUC) is the most common type of bladder malignancy in humans, but also in dogs that represent a naturally occurring model for this disease. Dogs are immunocompetent animals that share risk factors, pathophysiological features, clinical signs and response to chemotherapeutics with human cancer patients. This review summarizes the fundamental pathways for canine MIUC initiation, progression, and metastasis, emerging therapeutic targets and mechanisms of drug resistance, and proposes new opportunities for potential prognostic and diagnostic biomarkers and therapeutics. Identifying similarities and differences between cancer signaling in dogs and humans is of utmost importance for the efficient translation of in vitro research to successful clinical trials for both species.
Highlights
In 2021, it is estimated that approximately 65,000 men and 19,500 women will be diagnosed with bladder cancer (BlCa) in the US, with approximately 17,000 people succumbing to the disease [1]
The umbrella cells are characterized by a highly specialized apical plasma membrane, the asymmetric unit membrane (AUM), which is a component of the permeability barrier that protects underlying tissues from
The umbrella cells are characterized by a highly specialized apical plasma membrane, the asymmetric unit membrane (AUM), which is a component of the permeability barrier that protects underlying tissues from noxious components of urine
Summary
In 2021, it is estimated that approximately 65,000 men and 19,500 women will be diagnosed with bladder cancer (BlCa) in the US, with approximately 17,000 people succumbing to the disease [1]. For patients with recurrent or metastatic UC, cisplatin-based combination chemotherapy regimens are the standard of care for first-line therapy in patients who can tolerate it [3]. These protocols include MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin), CMV (cisplatin, methotrexate, and vinblastine) and GC (gemcitabine and cisplatin). Enfortumab vedotin, an antibody drug conjugate that links the microtubule inhibitor monomethyl auristatin E (MMAE) to an antibody to Nectin-4, a cell adhesion protein expressed on bladder tumor cells, has been approved since 2019 for patients with metastatic BlCa that progressed after treatment with both platinum-based first-line chemotherapy and second-line therapy with an immune checkpoint inhibitor [6,7]. Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor, was approved for patients with FGFR mutations that have progressed after chemotherapy [8]
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