Cisplatin Resistance and Metabolism: Simplification of Complexity.

Simple Summary: Prolonged cisplatin treatment can lead to acquired cancer cell resistance accompanied by various metabolic disturbances, which play an important role in maintaining homeostasis. In particular, resistant cells can regulate energy requirements and evade cisplatin-mediated toxicity via multiple metabolic adaptations. Here we discuss the existing evidence on metabolic alterations in cisplatin-resistant cells and their impact on the development of drug non-response. Cisplatin is one of the most well-known anti-cancer drugs and has demonstrated efficacy against numerous tumor types for many decades. However, a key challenge with cisplatin, as with any chemotherapeutic agent, is the development of resistance with a resultant loss of efficacy. This resistance is often associated with metabolic alterations that allow insensitive cells to divide and survive under treatment. These adaptations could vary greatly among different tumor types and may seem questionable and incomprehensible at first glance. Here we discuss the disturbances in glucose, lipid, and amino acid metabolism in cisplatin-resistant cells as well as the roles of ferroptosis and autophagy in acquiring this type of drug intolerance. [ABSTRACT FROM AUTHOR]