Compositions for Inhibitors of QSOX1 (No. 1642)
Lead Researcher: Prof. Deborah Fass
A potential target for anticancer drug design.Cancer is the second leading cause of death in the US, accounting for roughly 23% of all deaths (as of 2008), and with estimated cost of care of $157 billion (as of 2010). Despite major advances in the management of cancer, most types of solid tumors remain resistant to conventional treatment modalities. The local microenvironment, or niche, of a cancer cell plays important roles in cancer development. A major component of the niche is the extracellular matrix (ECM), a rich mesh of fibrous proteins surrounding cells that has been shown to exert a protective and supporting effect on cancer progression. Therefore, targeting the ECM represents a novel avenue for rational anticancer drug design. The current technology allows for specific targeting of an enzyme that takes part in ECM assembly and maintenance, and may provide a novel means for combating cancer progression and metastasis emergence.
A team of researchers at the Weizmann Institute have that a secreted disulfide bond catalyst known as Quiescin sulfhydryl oxidase 1 (QSOX1) is required for proper assembly of the ECM. The main substrates of QSOX1 within the ECM are laminins. Thus, cells lacking QSOX1 show poor incorporation of laminin into the ECM mesh, resulting in decreased cell adherence and perturbed cell migration. Notably, in some cancer types such as pancreatic and breast cancers, QSOX1 and the ECM components it produces are over-expressed. This suggests that modulation of QSOX1 activity may provide a novel means to combating cancer and metastasis. Treatment of cancer cells with a monoclonal QSOX1-targeting antibody effectively blocked cell migration and provides a novel strategy for cancer treatment by QSOX1 inhibition.