Moving beyond cisplatin resistance: mechanisms, challenges, and prospects for overcoming recurrence in clinical cancer therapy.

Cisplatin, a classical platinum-based chemotherapy agent, has been a frontline treatment for various cancers for decades. However, its effectiveness has been hindered by the development of resistance, leading to cancer relapse. Addressing this challenge is crucial for both clinical practice and research. Hence, the imperative to unravel the intricate mechanisms underpinning cisplatin resistance and to uncover novel strategies to overcome this barrier holds immense significance. Within this review, we summarized the classification of platinum agents, highlighting their roles in therapeutic landscapes. We discussed the diverse mechanisms behind cisplatin resistance, including diminished intracellular cisplatin accumulation, intracellular detoxification, DNA repair, autophagy responses, heat shock proteins, tumor microenvironment, cancer stem cells, epigenetic regulation, ferroptosis resistance, and metabolic reprogramming. Drawing from this comprehensive understanding, we offered a series of prospective solutions to surmount cisplatin resistance and consequently mitigate the specter of disease recurrence within the realm of clinical cancer therapy.