One of the major challenges in oncology today is the persistent growth and spread of cancer, even when diagnosed and treated early. Compounding this problem is cancer’s ability to adapt and develop resistance to treatment. As a result, primary therapies, often developed at great cost and effort, become less effective than intended. This often leads to unresectable tumors and metastatic disease, reducing treatment options and patient outcomes.
A key mechanism enabling this resilience is the overexpression of heparanase, an enzyme that degrades the extracellular matrix (ECM). This degradation releases growth factors and signaling molecules, triggering cascades that drive cancer cell proliferation, invasion, and metastasis. Moreover, heparanase overexpression is linked to the development of drug resistance, further complicating treatment.
Targeting heparanase offers a promising therapeutic strategy. Inhibiting this enzyme restores the integrity of the ECM, disrupting the tumor microenvironment and resulting in reduced tumor growth, metastasis, and angiogenesis. This underscores the enzyme’s central role in cancer progression and highlights the potential of heparanase inhibitors as effective anticancer therapeutics.
To address this need, researchers at Leiden University have developed a proprietary library of rationally designed heparanase inhibitors. These compounds are based on the enzyme’s natural substrate, heparan sulfate, and are designed to covalently bind to its active site, causing irreversible inhibition. Among these, the lead compound VL166 has demonstrated significant efficacy in reducing cancer aggression in preclinical in vivo murine models.
