Chrono-Adaptive Resistance Disruption (CARD): A Novel Pharmacological Framework to Address Anticancer Drug Resistance

Abstract

Drug resistance in anticancer therapy has long remained an open problem in biomedical and pharmacological research in oncology. Nevertheless, despite numerous efforts aimed at targeting biological mechanisms at the molecular and pathway levels and testing various combination therapies, the present pharmacological approach has remained largely stagnant and insensitive to changes in circadian rhythms of tumor biology and drug resistance. However, an emerging body of preclinical and clinical data suggests that circadian rhythms play a pivotal biological role in regulating drug metabolism, cell stress, DNA repair, and adaptive resistance mechanisms. This article introduces a conceptual framework termed Chrono Adaptive Resistance Disruption (CARD), and proposes a novel pharmacological strategy aimed at using circadian biology to control anticancer drug resistance. Unlike other approaches based on chronotherapies and/or resistance management, CARD focuses on proactive disruption of resistance trajectories based on time optimal drug regimens and adaptive pharmacological interventions. It provides a biological framework, supported by various preclinical and clinical data in the biomedical and pharmacological literature. Notably, to date, this combined strategy has not been explicitly conceptualized as an integrated framework in the biomedical and pharmacological literature, underlining the potential novelty and translational relevance of CARD.