**7. Conclusions**

GAGs are versatile molecules that play multifaceted roles in the human body. They are involved in all biological functions and are acrucial mediator of homeostasis. Alterations in both the expression and GAG fine chemical structure are evident during cancer development and progression. Research efforts directed at the role of GAGs in cancerogenesis are rapidly increasing, and some of the findings have made their way into clinical practice.

The field has been facilitated by essential developments in available technologies, including imaging technologies, mass spectrometry, microarrays, and bioinformatics tools [275–277]. Therefore, we can now deepen our studies of the glycome, leading to an improved understanding of the glycobiology field. Indeed, the recent advancements in the GAG structure/function relationship have allowed a better appreciation of the

GAGs role in tumorigenesis and the utilization of this knowledge for cancer detection, prognosis, and therapy implementation. GAGs are now being employed as biomarkers for disease progression and tumor aggressiveness [278].They are involved in the tumor immune response, can be used by themselves or in the form of hybrid PGs therapeutic targets, and offer targeted drug delivery [1,279]. As drug carriers, GAGs are characterized by high specificity, multi-functionality, and good biocompatibility, the key to the success of new therapies in oncology [279]. Considering that GAGs are critical molecules of the complex cellular and molecular TME network, their multi-factorial utilization could enable personalized therapy implementation. However, some obstacles still need to be overcome as the heterogeneity of native GAG preparations has introduced the need for producing synthetic or semi-synthetic GAG mimetics with improved pharmacokinetic properties, higher selectivity, and attenuated or even abolished adverse side-effects. Future research efforts will enhance GAG implementations in the clinic and hopefully improve therapeutic strategies for some cancer types.

**Author Contributions:** Conceptualization, D.N.; writing—original draft preparation, D.N., M.N., A.B., E.-M.G. and A.K.; writing—review and editing, D.N., A.M.T. and G.N.T. All authors have read and agreed to the published version of the manuscript.

**Funding:** D.N. was partially funded by the Research Committee of University of Crete (ELKE), grant number (KA:10028), M.N. was partially funded by UEFISCDI grant number (PN-III-P1-1.2-PCCDI-2017-0341/2018).

**Acknowledgments:** This article is part of the Innogly Cost action initiative.

**Conflicts of Interest:** The authors declare no conflict of interest.
