**6. Concluding Remarks**

Fucoidans are a family of sulphated polysaccharides with grea<sup>t</sup> diversity in their structures due to their di fferent sulphation patterns and the types of monosaccharides that in addition to fucose make up their backbone.

In some cancer types, fucoidans can inhibit metastasis processes including EMT, migration, invasion and MET processes. Fucoidans function by altering signaling axes such as TGFR/TGF-β, PI3K/AKT, VEGF, NF-κB, or ERK1/2 pathways and by inhibiting MMPs from cancer cells. Other mechanisms in which fucoidans may prevent EMT are TGF-β inhibition regulation of microRNAs. However, many questions regarding the functional mechanisms in which fucoidans a ffect EMT remain, leaving the door open for future research.

The molecular characteristics of fucoidans (e.g., molecular weight and sulphation grade) enable chemical or enzymatic modifications, which make them good candidates for therapeutic use, or to use them as adjuvants to increase the therapeutic e fficiency of known chemotherapeutics. Moreover, the molecular versatility of fucoidans has made them excellent precursors for the development nanoparticles. Studies have demonstrated their potential to improve the e fficiency of drug delivery into the tumor and/or to achieve a synergistic e ffect with other cancer drugs.

However, despite these auspicious/promising results, there is a lack of information about fucoidan structure, molecular weight, sulphate amount, etc. This will be important to better understand the possible influence of fucoidans on intracellular biological activity. In addition, the use of fucoidans in di fferent cancer models and the interpretation of the results remains challenging. Most of the time, there are controversies related to the vague establishment of the studying variables or the scarce explanation of them, which makes it di fficult to compare di fferent studies.

Although there are still multiple challenges to overcome before fucoidans can be clinically used, it is predicted that in the near future, fucoidan-based approaches may provide important advances in overcoming the most complicated cancer drawbacks including metastasis and drug resistance and improving chemotherapy response and quality of life in cancer patients. Further studies are needed to discover more fucoidans and fucoidan-related targets to acquire a better understanding of how these molecules can arrest the mechanisms of metastasis and multidrug resistance in di fferent cancer types.

**Author Contributions:** Conceptualization, M.E.R., I.R., P.B.; Validation, M.E.R., I.R., T.S., P.L., P.B.; Formal analysis, M.E.R., I.R.; Data curation, M.E.R., I.R., L.Z., T.S., P.L.; Writing—original draft preparation, M.E.R., I.R.; Writing—review and editing, M.E.R., I.R., L.Z., T.S., P.L.; Visualization, M.E.R., I.R.; Supervision, P.B. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by National Commission for Scientific and Technological Research (CONICYT) Grant 21201835 (MER). National Funding for Scientific and Technologic Development of Chile (FONDECYT) Grant 11150802 (PB), National Funding for Scientific and Technologic Development of Chile (FONDECYT) Grant 3170826 (IR).

**Acknowledgments:** The authors want to thank Hannah Desmond for her help in editing the English for this article. **Conflicts of Interest:** The authors declare no conflict of interest.
