
In recent years, ADCs have emerged as a transformative therapeutic modality in oncology, offering a promising avenue for the treatment of bladder cancer. ADCs combine the specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic agents, enabling targeted delivery of payloads to tumor cells while sparing healthy tissues. This unique mechanism of action has led to significant advancements in the treatment landscape, particularly for cancers that are resistant to conventional therapies (5). In bladder cancer, ADCs have demonstrated remarkable efficacy by targeting specific tumor-associated antigens, such as nectin-4 and HER2, thereby inducing tumor cell apoptosis and inhibiting metastasis. For example, Enfortumab vedotin (targeting NECTIN-4) achieved a median overall survival of 12.9 months in the EV-301 trial (vs. 9.0 months with chemotherapy) (6). Similarly, trastuzumab deruxtecan, a HER2-directed ADC, has demonstrated promising antitumor activity in HER2-expressing bladder cancer (7), offering a potential therapeutic option for this subset of patients.
Despite these promising developments, several challenges persist in the clinical application of ADCs for bladder cancer. Key issues include the durability of therapeutic responses, the management of off-target toxicities, and the heterogeneity of antigen expression across different patient subtypes (8). Moreover, the optimal integration of ADCs with existing treatment paradigms, such as immune checkpoint inhibitors and chemotherapy, remains an area of active investigation (9). Addressing these challenges is crucial for maximizing the therapeutic potential of ADCs and improving patient outcomes.
This study provides a comprehensive evaluation of the current landscape of ADC-based therapies for bladder cancer, with a focus on their mechanisms of action, clinical efficacy, and safety profiles. We systematically review ongoing clinical trials, highlighting the most promising ADC candidates and their respective targets. Furthermore, we explore emerging strategies to enhance the precision and durability of ADC therapies, including the development of novel linkers, payloads, and antibody engineering techniques. By synthesizing the latest clinical data, this review aims to offer valuable insights into the future directions of ADC research and their potential to revolutionize bladder cancer treatment. Our findings underscore the importance of continued innovation in ADC technology and the need for personalized approaches to overcome the limitations of current therapies, ultimately paving the way for more effective and safer treatment options for patients with bladder cancer.