This article addresses the multifaceted problem of drug resistance in cancer therapy. The authors articulate a framework for understanding resistance by defining its key biological determinants, including tumor burden and growth kinetics, heterogeneity, physical barriers, the immune system, and undruggable genomic drivers. They propose four general solutions to overcome resistance: earlier detection of tumors, achieving deeper therapeutic responses, continuous monitoring and adaptive interventions during therapy, and mapping cancer cell dependencies. The article emphasizes that drug resistance is the primary obstacle to curing cancer and suggests that integrating new technological and pharmacological approaches offers a pathway to more effective, individualized treatment strategies.
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