Estratègies terapèutiques pel tractament de la metàstasi: la metal·loproteinasa com a potencial diana biològica

Abstract

Nowadays metastasis continues to be one of the leading causes of death in cancer patients and the number of cases increases over the years. Treatment of this disease is difficult, because it can develop differently depending on the patient and because it is often detected in advanced stages, when the tumor cells have already spread to other tissues. Metastasis usually occurs in late stages of cancer and it can be related to advanced tumors or large primary neoplasms. This disease proceeds in different phases, in which tumor cells migrate from the primary tumor to the target organ, where they form a secondary tumor. This can be caused by some factors and it has been seen, that there are many molecules involved in metastasis progression. Therefore, the treatment of this illness is especially focused on inhibiting these molecules and the initial stages of the metastatic process. Metalloproteinases (MMPs) are one of the main molecules involved in metastasis, which can remodel the extracellular matrix (ECM) in the primary tumor and allow the dispersion of malignant cells. Moreover, these proteins can also promote the formation of a premetastatic niche in the target organ, in order to facilitate tumor cell colonization. Most of the strategies and clinical trials that have been used so far for inhibiting metastasis and MMPs, have not been very successful. In this work, it has been analysed other strategies that are under development to inhibit metastasis such as: nanoparticles, biomarkers, immunotherapy or antibiotics. In particular, to inhibit MMPs it has been analysed chemical inhibitors, gene expression inhibitors, antibodies and nanoparticles. In general they have demonstrated high potential in in vitro and in vivo models, but they are still in preclinical phases or in clinical trials in phase I, III or in patient recruitment. Unfortunately, metastasis treatment remains a challenge and strategies to eradicate it are still needed. Because of that, it is important to know all the processes and the functions of all molecules involved, and to achieve a more selective and specific inhibition of these molecules. In addition, strategies based in the prevention of this illness are of great interest, in order to detect metastasis in earlier stages