Underlying Mechanisms for Distant Metastasis - Molecular Biology.

BACKGROUND The formation of distant metastases constitutes a complex process with a variety of different genes and pathways involved. To improve patient survival, it is necessary to understand the underlying mechanisms of metastasis to allow for targeted intervention. METHODS This review provides an overview of the general concepts of metastasis, focusing on the most important genes and pathways involved and on interventional strategies. RESULTS Cancer cells undergo different steps to form metastasis: most prominently, local invasion, intravasation, survival in the circulation, arrest at a distant organ site and extravasation, micrometastasis formation, and metastatic colonization. In order to pass these steps, different molecular pathways are of major importance: EGF/RAS/RAF/MEK/ERK, PI3K/Akt/mTOR, HGF/Met, Wnt/β-catenin, and VEGF signaling. The HGF/Met regulator MACC1 and the Wnt signaling target S100A4 have been shown to play a major role in the metastatic process. Each gene and pathway provides an opportunity for therapeutic intervention. CONCLUSION Since metastasis represents a highly limiting factor in cancer therapy causing 90% of cancer deaths, it is imperative to reveal the underlying mechanisms. This is fundamental for uncovering prognostic markers and new targeted therapy options.