Adaptation of mitochondria in drug resistance of cancer: frequency, mechanisms, and control

Cancer treatment is severely restricted by drug resistance, and numerous aspects of tumor characteristics, including drug resistance, are influenced by mitochondria, the primary organelle for cellular energy supply. These organelles can undergo rapid dynamic alterations and integrate cellular signaling networks, providing cancerous cells with bioenergetic and metabolic flexibility. For many cancer types, focusing on mitochondria for cancer treatment and overcoming drug resistance has gained more attention. Several mitochondrial adaption systems, including mitochondrial dynamics, metabolic processes, and the apoptotic regulatory machinery, have been identified as possible targets. Recent developments in the science of mitochondria have shown the inaccessibility of their targeting, their unclear roles in tumor biology, and the complexity of their organization and functions have complicated the clinical application of mitochondrial-based cancer therapeutic approaches. It is critically necessary to find new mitochondria-targeting drugs and innovative mitochondria-targeting strategies. This chapter discusses the molecular mechanisms underlying mitochondrial stress adaption and its intricate connection to resistance to cancer treatments.