Introduction: Matrix metalloproteinase (MMP)-2 is a zinc-dependent proteinase that is capable of cleaving all extracellular matrix (ECM) substrates. Degradation of the matrix is a key event in the progression, invasion, and metastasis of potentially malignant and malignant lesions of the head and neck. Therefore, blocking MMP-2 expression or activity may present a promising strategy for anticancer treatment. Areas covered: Current understanding of the molecular mechanisms that govern MMP-2 regulation and its tumorigenic effects, and that are involved in the initiation and progression of head and neck cancers, in particular the emerging role of MMP-2 in cell migration, which is a prerequisite for tumor metastasis. MMP-2 gene polymorphisms, cellular substrates, and interacting proteins are summarized. The current state of drugs that target this enzyme, either alone or in combination with other targeted agents are also discussed. Expert opinion: MMP-2 has long been a drug target. The current status of MMP-2 inhibitors as anticancer agents and their failure in the clinic is discussed in light of new data on the MMP-2s role as a cell surface transducer-data that may lead to the design and development of novel, MMP-2-targeting inhibitors.
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