Moving targets: Emerging roles for MMPs in cancer progression and metastasis

•Protease-independent functions of MMPs may contribute to cancer progression.•Innovative imaging tools facilitate detection of MMP activity in vivo.•MMP activity can be harnessed to improve cancer therapy.•MMPs also function as negative regulators of therapy response in cancer.•MMPs contribute to metastasis even before tumor cell dissemination occurs.

Matrix metalloproteinases have long been associated with cancer. Clinical trials of small molecule inhibitors for this family of enzymes however, were spectacularly unsuccessful in a variety of tumor types. Here, we discuss some of the newer roles that have been uncovered for MMPs in cancer that would not have been targeted with those initial inhibitors or in the patient populations analyzed. We also consider novel ways of using cancer-associated MMP activity for clinical benefit.