Photodynamic Therapy Targeting Matrix Metalloproteases in Cancer: Standpoint for an Innovative Anticancer Strategy

Matrix metalloproteases (MMPs), which are activated during malignancy growth and metastasis, have been a focus of current anticancer research and development. The selective recognition and precise inhibition of active MMPs could limit cancer progression. Photodynamic therapy (PDT) is a well-established local treatment for solid tumors. MMPs are expressed primarily in the vicinity of the tumor, and PDT strongly influences this process. However, in rare cases, PDT can activate MMPs. An improved PDT outcome was observed with the action of an MMP inhibitor (MMPI), namely Prinomastat. Research on this topic remains limited, presenting a substantial opportunity for further investigations. Various small-molecule compounds have been designed to target MMPs as potential inhibitors, but clinical trials have not confirmed their efficacy in vitro or in vivo. Currently, novel MMPIs with complex chemical structures are being designed and have shown high efficacy in initial preclinical studies. This review aims to provide a critical overview of recent advances in the use of cancer-related MMPs as therapeutic targets, along with new innovative approaches to targeting them. The effects of PDT on cancer-related MMPs, along with the advantages of combining therapies that could enhance curative efficacy, are discussed. The novel inhibitory approaches that regulate cancer-related MMPs are summarized.