The promising arsenal of ferroptosis inducers in bladder cancer.

Bladder cancer ranks among the most common malignancies of the urinary system. Despite continuous advances in treatment technologies, the risk of tumor progression and metastasis remains high due to its extreme heterogeneity, resulting in poor patient prognosis. Patients with muscle-invasive bladder cancer face the greatest challenges. Immediate clinical treatment is radical cystectomy after the administration of neoadjuvant therapy. The effect of different conventional chemotherapeutic drugs is heavily impaired by tumor resistance. In turn, the research of effective therapeutic approaches to prevent resistance of malignant tumors has turned out to be the most important clinical concern in the management of bladder cancer. Ferroptosis is another type of programmed cell death that is morphologically and mechanistically different than apoptosis and necrosis. To maintain high rates of proliferation, bladder cancer cells are hypernormal to iron-dependent oxidative stress. So using the ferroptosis inducers to destabilize their vulnerable antioxidant defenses provides a very specific targeting approach to the weaknesses of this natural metabolic homeostasis. Inductors of ferroptosis (erastin, artemisinin, conjugated polymer nanoparticle, quinazoline-aromatic urea analogue derivatives, etc.) show great potential in improving the efficacy of traditional anticancer drugs used to fight against bladder cancer. Preclinical studies combining standard therapies with ferroptosis-related treatments have yielded promising results. However, clinical trials targeting ferroptosis in bladder cancer remain scarce, posing challenges for translating these findings into clinical practice. In this review, we aim to highlight the latest advances in ferroptosis induction as a therapeutic strategy for bladder cancer. It provides a reference for subsequent research and additional insights into the development and validation of corresponding drugs for bladder cancer treatment.