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Role of MMPs in metastatic dissemination: implications for therapeutic advances
D Raffo1, O Pontiggia, M Simian
1Instituto de Oncologia Ángel H. Roffo, Av. San Martín 5481, Buenos Aires, Argentina.
Abstract:
Matrix metalloproteinases (MMPs) have been implicated in both normal and pathologic processes. In cancer in particular, in vitro and animal studies showed an involvement of MMPs in many stages of cancer progression. This led to the development of MMP inhibitors that in most cases failed in clinical trials. In this review we go over the role of MMPs in the different stages of cancer progression and try to understand why the early generation of MMP inhibitors failed. The analysis of the lessons from this first experience, plus the review of the current knowledge that shows that MMPs may be pro-or anti-tumorigenic may set the stage for a future success for this therapeutic strategy in cancer.
Insights
Matrix metalloproteinases (MMPs) are crucial in cancer progression. Understanding why early MMP inhibitors failed is key to developing future cancer therapies targeting these enzymes.
Area of Science:
- Oncology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) play roles in normal and pathological processes.
- MMPs are implicated in various stages of cancer progression based on in vitro and animal studies.
Purpose of the Study:
- To review the role of MMPs in different cancer progression stages.
- To analyze the reasons for the failure of early MMP inhibitor clinical trials.
- To discuss future therapeutic strategies for cancer targeting MMPs.
Main Methods:
- Literature review of MMPs in cancer progression.
- Analysis of clinical trial data for MMP inhibitors.
- Synthesis of current knowledge on MMPs' dual role (pro- or anti-tumorigenic).
Main Results:
- MMPs are involved in multiple facets of cancer development.
- Early MMP inhibitors demonstrated limited efficacy in clinical settings.
- MMPs can exhibit both pro-tumorigenic and anti-tumorigenic functions.
Conclusions:
- Lessons learned from failed MMP inhibitor trials are critical.
- The complex, context-dependent role of MMPs necessitates nuanced therapeutic approaches.
- Future MMP-targeted cancer therapies may succeed by considering their dual functions.
