Harnessing the quinoline core for targeted cancer therapy.

The quinoline nucleus is a privileged scaffold valued for its structural plasticity and synthetic accessibility. This review systematically summarizes advances in quinoline derivatives for targeted cancer therapy from 2017 to 2026, organized by major molecular target families - including kinases, metabolic enzymes, epigenetic regulators, drug transporters, and others - with emphasis on rational design, key structure-activity relationships (SARs), and antitumor efficacy. Despite progress, challenges such as isoform selectivity, suboptimal pharmacokinetics, and drug resistance persist; future efforts should focus on dual-targeting and prodrug strategies to overcome these limitations. This review aims to provide medicinal chemistry insights for the design of next-generation quinoline-based anticancer agents with improved selectivity, pharmacokinetic properties, and ability to overcome drug resistance.