The 1,2,4-triazole scaffold has emerged as a privileged heterocyclic core in the development of anticancer agents due to its unique physicochemical properties, bioavailability, and diverse biological activities. Over the past few years, significant advancements have been made in the design and structural optimization of 1,2,4-triazole-based anticancer compounds, with a strong focus on their structure-activity relationships (SARs). This review provides a comprehensive overview of the latest developments (2022-2025) in 1,2,4-triazole-containing anticancer agents, emphasizing their mechanisms of action, molecular targets, and therapeutic potential. The discussion encompasses the various modifications introduced into the 1,2,4-triazole core, exploring their impact on anticancer efficacy, selectivity, and pharmacokinetic properties. In particular, recent studies have highlighted the ability of these derivatives to inhibit key cancer-related enzymes (such as kinases, carbonic anhydrases, and topoisomerases), interfere with DNA interactions, and modulate apoptotic and autophagic pathways. This review also presents emerging SAR trends, highlighting key functional group modifications that enhance anticancer potency while minimizing off-target effects. Furthermore, recent in vivo studies and clinical evaluations of promising 1,2,4-triazole derivatives are discussed to assess their translational potential. Lastly, we outline future research directions and challenges in the development of next-generation triazole-based anticancer agents, aiming to bridge the gap between rational drug design and clinical application. This comprehensive analysis underscores the critical role of the 1,2,4-triazole pharmacophore in anticancer drug discovery and provides valuable insights for the design of more potent and selective anticancer therapeutics.
