Matrix metalloproteinases: Potential therapy to prevent the development of second malignancies after breast radiotherapy

Radiotherapy is widely used in the treatment of patients with breast cancer, but ionizing radiation-induced carcinogenesis has been described in several studies. Matrix metalloproteinases (MMPs) are a wide family of proteases secreted by tumour and microenvironmental cells that are directly linked with invasion and metastasis through complete extracellular matrix (ECM) breakage. In the past decade, MMPs have been associated with other carcinogenesis steps, including tumour growth and angiogenesis promotion. Moreover, in vitro studies have demonstrated an enhanced migration, invasiveness, and angiogenic ability of cancer cells after radiation exposure through an increase in MMP activity. These findings are consistent with clinical observations of breast cancer metastases raised in bone, lung and brain tissues after radiotherapy. The aim of this review was to analyse the current state of research on MMPs and report new insights into the potential of MMP-targeted therapy in combination with radiotherapy to decrease the risk of radiation-induced second malignancies and to improve the overall survival of breast cancer patients. (C) 2012 Elsevier Ltd. All rights reserved.