[Biology of metastases and molecular mechanisms of their formation]

Metastasis in cancer patients is often associated with a poor prognosis. However, we still have limited knowledge of the underlying molecular mechanisms, due to the great complexity of the biological processes involved in the formation of metastases. During tumor progression, the metastatic cells acquire genetic and epigenetic modifications allowing them to adapt to the various environments they will encounter (in the circulation and the host microenvironment) and to resist to the antitumor therapeutic agents. In this review, we expose the current knowledge on the biology of metastases. We summarize the different signaling pathways involved in the successive steps of the metastatic cascade, highlighting recent advances in the field to better understand the molecular mechanisms leading to metastasis formation. In addition, our understanding of metastatic progression has made great progress with the recent advances in high throughput sequencing techniques. We expose data from genomic analyzes of metastases. These studies allowed the identification of alterations acquired exclusively in distant metastases. They highlight the emergence of alterations offering new targeted therapeutic options for cancer patients and they provide new insight into the mechanisms of treatment resistance at the origin of metastatic relapses. Finally, we present latest clinical trials based on the genomic profiles of metastases, initiated in recent years, and we discuss their potential impact in personalized medicine.