Maykon Jhuly Martins de PAIVA, Márcio TREVISAN, Sávia Denise Silva Carlotto HERRERA, Taides Tavares dos SANTOS, Juliane Farinelli PANONTIN, Walmirton Bezerra D'ALESSANDRO
Eurasian Journal of Medicine and Oncology - 2026;10(4):1-18
Cancer remains a major global health burden driven by complex molecular alterations that challenge current therapeutic strategies. Plant-derived alkaloids, characterized by remarkable structural diversity and multitarget biological activity, have emerged as promising candidates in anticancer drug discovery; however, despite substantial preclinical evidence, their clinical translation remains limited. This review synthesizes current knowledge on the molecular mechanisms underlying the anticancer effects of these compounds, including modulation of microtubule dynamics, induction of apoptosis, DNA damage, and regulation of oncogenic signaling pathways such as PI3K/Akt/mTOR and NF-kappaB. Evidence from in vitro and in vivo studies is critically examined, highlighting both potent cytotoxic activity and variability in pharmacological responses, while distinguishing mechanistic causality from associative observations in light of experimental design limitations, particularly the predominance of in vitro models and lack of standardized methodologies. Key translational barriers are further discussed, including toxicity, pharmacokinetic instability, and the limited predictive value of current preclinical models. In this context, we propose that integrating mechanistic pharmacology with innovative translational frameworks is essential to enhance the clinical applicability of alkaloid-based therapies. Collectively, these insights reinforce the potential of plant-derived alkaloids as multitarget anticancer agents and underscore the need for integrative strategies to bridge the gap between experimental efficacy and clinical application.
