Heparanase as a therapeutic target for mitigating cancer progression

Abstract

Cancer has been one of the primary causes of mortality for the last three decades across the globe, with contemporary treatment modalities often falling short due to limitations viz. drug resistance, toxicity, and the inability to target molecular mechanisms of tumor progression. Among various intracellular mediators implicated in cancer progression, heparanase, a heparan sulfate degrading enzyme, has been pivotal by facilitating tumor invasion, angiogenesis, and metastasis. Inhibiting the activity of heparanase is a promising therapeutic approach that can potentially curtail tumor growth and metastasis, offering a novel strategy to curb cancer progression. The present review underpins the discovery, structural features, and functional roles of heparanase, with a focus on its differential expression in normal and cancer cell state. Further, the review provides an insight in several classes of heparanase inhibitors including nucleic acid-based inhibitors, polysulfated saccharides, vaccines, miRNA, monoclonal antibodies, natural compounds and small molecule inhibitors along with their mechanism of action and potential benefits in cancer therapy. Recent advancements in heparanase inhibitor development, especially those agents that have moved into clinical trials and received patents is also highlighted thereby underscoring their therapeutic potential and commercial viability. The present review emphasizes over the potential of heparanase as a therapeutic agent and provides an extensive summary of actual endeavors to develop effective inhibitors that may substantiate the forthcoming landscape of cancer treatment.