Natural bioactive compounds: a potential therapeutic strategy to sensitize bladder cancer to cisplatin treatment?

Bladder cancer (BC) is the tenth most common cancer, and its incidence is steadily rising worldwide, with the highest rates in developed countries. Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the standard therapy for patients with muscle-invasive bladder cancer. However, less than 50% of patients initially respond to this treatment and nearly all of them eventually develop resistance, which is an important barrier to long-term survival. Therefore, there is an urgent need to understand the mechanisms of cisplatin resistance in BC and develop ways to counteract them. Several preclinical studies have demonstrated that naturally derived bioactive compounds, such as phytochemicals and flavonoids, can enhance the antitumor activity of cisplatin, with minimal side effects, by targeting different pathways involved in cisplatin sensitivity and resistance. However, their poor bioavailability has been one of the main problems for their successful introduction into clinical practice. At present, however, many new formulations with greatly increased bioavailability are under study in several clinical trials with encouraging results.