Naringenin in Cancer Therapy: Molecular Mechanisms, Signaling Networks, and Translational Perspectives

Cancer remains a significant global health challenge, underscoring the need for active therapeutic strategies that target the key molecular determinants of tumor progression. Naringenin, a flavonoid prevalent in the diet and abundant in citrus fruits, has emerged as a promising anticancer agent due to its ability to regulate multiple oncogenic signaling pathways involved in cancer initiation, progression, and therapeutic resistance. This review highlights the molecular mechanisms through which naringenin modulates essential signaling networks, such as the PI3K/Akt/mTOR, NF-κB, MAPK, and TGF-β pathways, thereby suppressing cancer cell proliferation, inducing apoptosis, inhibiting angiogenesis, and preventing metastatic spread. Compared with previous reviews that mainly summarized the general pharmacological properties of naringenin, this review provides an integrated and critical analysis of cancer-related signaling networks, chemoresistance, therapeutic combinations, and emerging translational strategies. Importantly, it highlights the persistent gap between promising pre-clinical results and limited clinical evidence, and it emphasizes the pharmacokinetic, bioavailability, and safety challenges that need to be addressed for clinical translation. Finally, we highlight the existing challenges, knowledge gaps, and future perspectives for clinical translation to encourage the development of naringenin-based cancer therapeutics.