Theranostic Applications of Glycosaminoglycans in Metastatic Renal Cell Carcinoma

SIMPLE SUMMARY: Glycosaminoglycans (GAGs) are a class of carbohydrates that has been closely associated with cancer progression. GAGs have been implicated in cancer cell growth and are known to be involved in cell signaling. As GAGs are present in the extracellular matrix that surround tumor cells (tumor environment), they are intricately involved in the processes of cell migration and invasion, which are crucial for metastasis (spread to distant organs) to take place. Hence, the significance of this review is to explore the potential use of GAGs as biomarkers and therapeutic targets for metastatic renal cancer, which has poor rates of survival and faced with major challenges, that include lack of precise monitoring of disease treatment and effective treatment strategies with minimal toxicity. ABSTRACT: Renal cell carcinoma (RCC) makes up the majority of kidney cancers, with a poor prognosis for metastatic RCC (mRCC). Challenges faced in the management of mRCC, include a lack of reliable prognostic markers and biomarkers for precise monitoring of disease treatment, together with the potential risk of toxicity associated with more recent therapeutic options. Glycosaminoglycans (GAGs) are a class of carbohydrates that can be categorized into four main subclasses, viz., chondroitin sulfate, hyaluronic acid, heparan sulfate and keratan sulfate. GAGs are known to be closely associated with cancer progression and modulation of metastasis by modification of the tumor microenvironment. Alterations of expression, composition and spatiotemporal distribution of GAGs in the extracellular matrix (ECM), dysregulate ECM functions and drive cancer invasion. In this review, we focus on the clinical utility of GAGs as biomarkers for mRCC (which is important for risk stratification and strategizing effective treatment protocols), as well as potential therapeutic targets that could benefit patients afflicted with advanced RCC. Besides GAG-targeted therapies that holds promise in mRCC, other potential strategies include utilizing GAGs as drug carriers and their mimetics to counter cancer progression, and enhance immunotherapy through binding and transducing signals for immune mediators.