The more advanced form of bladder cancer (BC), muscle-invasive bladder cancer (MIBC), remains a significant clinical challenge in both canine and human patients afflicted with the disease. Although non-muscle invasive bladder cancer is the more dominant subtype, cases often reccur or progress, even after treatment. Despite current treatment options like chemotherapy, cystectomy, and external beam radiation, invasive bladder cancers have poor prognosis, with a 50% mortality rate in humans, and dogs are rarely cured. Dogs naturally develop bladder cancer in the presence of a complete immune system, making them an ideal preclinical model for studying human bladder cancer and developing novel targeted therapies as opposed to current available murine models. This study investigated the potential of radiolabeled FDA-approved monoclonal antibodies dual-targeting EGFR1 and EGFR2 biomarkers for treating canine bladder cancer and the possibility of eventually translating these findings into human treatment.This thesis project aimed to characterize EGFR1 and EGFR2 expression in five different canine bladder cancer cell lines using technetium-99m binding assays, and confirming the binding affinities of monoclonal antibodies cetuximab and trastuzumab for these receptors. Colony formation assays were conducted to assess the impact of radiation therapy using beta-particle therapy (Lu-177-[cetuximab/trastuzumab]) and were compared with results from studies performed without radiation. Findings suggested that the antibodies alone do not have an inhibitory or proliferative effect on the canine bladder cancer and that any theraputic effects may be attributed to that of the radiation alone. Additionally, this study supports the use of targeting radiation therapy as a more promising treatment for both canine and human bladder cancer, with the potential for reduced off-target effects when compared to traditional radiation therapies, like external beam radiation therapy. The utilization of pet dogs as a model for MIBC is particularly advantageous, given that canine bladder cancer closely resembles the disease in humans. Overall, this approach could accelerate the development of targeted radiotherapies and improve treatment outcomes for both veterinary and human patients. Leveraging similarities between canine and human bladder cancer should allow for enhanced therapeutic strategies that expedite the translation of novel therapeutics into clinical practice, a win-win scenario for canine and human patients alike.
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