Fucoidan-Based Combination Strategies in Cancer Therapy: Biological Basis, Current Evidence, and Future Perspectives.

Combination therapy has emerged as an effective strategy to enhance anticancer efficacy while overcoming the limitations of conventional cancer treatment, including systemic toxicity and therapeutic resistance. Among marine-derived bioactive compounds, fucoidan, a sulfated polysaccharide isolated from brown seaweeds, has attracted considerable attention because of its multitarget biological activities, favorable safety profile, and ability to enhance therapeutic responses. Increasing evidence suggests that fucoidan may be particularly valuable as a multifunctional combination partner rather than as a standalone anticancer agent, capable of potentiating the efficacy of conventional chemotherapy, targeted therapy, and, to a much lesser extent, natural bioactive compounds. In this review, we summarize the biological characteristics that make fucoidan an attractive combination partner and provide a comprehensive overview of current evidence regarding fucoidan-based combination strategies for cancer therapy. We further discuss the molecular mechanisms underlying these combination effects, including the regulation of apoptosis, autophagy, tumor microenvironment remodeling, and oncogenic signaling pathways associated with therapeutic resistance. Although combinations with conventional anticancer therapies have been extensively investigated, studies involving natural bioactive compounds remain remarkably limited, highlighting an important opportunity for future research. Collectively, current evidence, derived largely from preclinical studies, supports the potential of fucoidan as a promising multifunctional adjuvant for cancer combination therapy, while further standardization, mechanistic studies, and clinical validation will be essential for its successful translation into clinical practice.