Unlocking New Possibilities: Antibody-Drug Conjugates for Bladder Cancer Targeted Therapy

: Bladder Cancer (BC) ranks as the tenth most prevalent cancer globally. The most frequently occurring form of bladder cancer is Urothelial Carcinoma (UC), which represents ۹۰% of bladder cancer cases in both USA and Europe. Historically, treatment options for second-line therapy in bladder cancer have been limited. Chemotherapy regimens often resulted in suboptimal responses and significant toxicity. However, the advent of immune checkpoint inhibitors and targeted therapies like Antibody-Drug Conjugates (ADCs) has transformed the therapeutic landscape. Method: We conducted a narrative review to identify relevant studies on ADCs in BC and specifically UC treatment. The search was performed using two major databases, PubMed and Google Scholar to capture a broad range of scientific articles. The search terms included combination of keywords such as “bladder cancer”, “antibody-drug conjugate” and “targeted therapy”. Results: ADCs represent a groundbreaking advancement in the treatment of UC. By combining the specificity of monoclonal antibodies with potent cytotoxic agents, ADCs enable targeted delivery of chemotherapy directly to cancer cells. This targeted approach minimizes damage to healthy tissues and enhances treatment efficacy, making ADCs a promising therapeutic option in the evolving landscape of BC management. ADCs work through a mechanism known as receptor-mediated endocytosis, where the antibody component binds to specific antigens expressed on the surface of cancer cells. Upon internalization, the cytotoxic drug is released, leading to cell death. One notable example is enfortumab vedotin, which targets nectin-۴, a protein overexpressed in many UCs. Clinical trials have demonstrated that enfortumab vedotin not only shows acceptable tolerability but also promising efficacy, with response rates exceeding ۴۰% in patients. Another promising ADC is sacituzumab govitecan, which targets Trop-۲, a protein frequently expressed in various solid tumors, including UC. Sacituzumab govitecan has shown encouraging results in clinical trials, providing a new treatment option for patients with advanced disease. The success of these agents underscores the potential of ADCs to improve outcomes in a patient population that has historically faced poor prognoses. While several ADCs are currently under investigation specifically for UC, their development reflects a broader shift towards personalized medicine, where therapies are tailored based on the specific characteristics of the tumor, by identifying biomarkers that can predict responses to ADCs, enhancing patient selection and optimizing treatment strategies. For instance, studies are exploring combinations of ADCs with immune checkpoint inhibitors to harness synergistic effects and improve overall efficacy. Furthermore, the development of next-generation ADCs aims to refine the therapeutic index by improving linker technology and payload potency, potentially leading to even better outcomes with reduced side effects. As we gain a deeper understanding of tumor biology and the mechanisms of action of these agents, ADCs hold the potential to become integral components of standard treatment protocols for BC. Conclusion: conclusively, ADCs represent a transformative approach in the management of UC, offering new hope to patients battling this challenging disease. With ongoing research, these innovative therapies may soon be standard practice, significantly enhancing survival and quality of life for individuals affected by BC.

کلیدواژه ها:

bladder cancer ، antibody-drug conjugate ، targeted therapy