Figure (2). Mechanisms and therapeutic strategies of therapy-induced tumor resistance.

Therapy induces the emergence of DTPCs, which can survive initial treatment and subsequently expand to drive tumor relapse. These persister cells utilize multiple survival mechanisms, including genetic mutations, epigenetic reprogramming, metabolic rewiring, phenotypic plasticity, and support from the tumor microenvironment. MRD and ctDNA monitoring enable early detection of relapse by identifying residual disease. Insights into persister cell biology and MRD dynamics can help guide the development of resistance-overcoming therapies, such as epigenetic interventions, metabolic targeting, immune checkpoint blockade, and rational combination approaches.