Systematic Reversal of Drug Resistance in Cancer

Drug resistance in cancer is a significant contributor to high mortality, and it exists in the complex form of a multi-parameter. Here, we unravel the roles of tumor heterogeneity, intratumoral physiological barriers, and safe havens in the onset and progression of cancer drug resistance, and outline strategies for resolution. We advocate for a “three-step approach” to reverse cancer drug resistance, including the management of cancer evolution and early intervention, the normalization of intratumoral physiological barriers, and the breakage of tumor safe havens. This approach aims to effectively manage the source of drug resistance, dismantle the breeding grounds of drug resistance, and break the sanctuaries where drug resistance hides.