Abstract
Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that has garnered significant attention due to its potential multiple antitumor mechanisms. This review first explores the current statuses and challenges faced in tumor prevention and treatment, pointing out the toxic side effects of traditional chemotherapy and radiotherapy as well as the issue of drug resistance in tumor cells, particularly adverse reactions such as decreased immune function caused by chemotherapy and radiotherapy. It further analyzes the relationship between inflammation, immune evasion in the tumor microenvironment, and tumor growth and metastasis. Subsequently, it discusses multi-target therapy strategies, introducing PEA as an emerging therapeutic candidate whose anti-inflammatory, pro-apoptotic, anti-angiogenic, and antioxidant effects show great promise in tumor prevention and treatment. Preclinical research and preliminary clinical trial results indicate its safety and efficacy, supporting its role as an adjunct in tumor treatment. In addition, innovative explorations that combine modern drug delivery systems with combination therapy strategies are proposed, aiming to enhance the bioavailability and therapeutic effectiveness of PEA. Finally, the future of personalized precision treatment and combination therapy models is anticipated to bring new hope for tumor prevention and treatment.