[Tumor microenvironment and therapeutic resistance process]

Over the last decade, it has become clear that cancer is not just a disease of the genes, and that the tumor microenvironment (TME) plays an important role in cancer progression. Interactions between tumor cells and the TME, made of the extracellular matrix (ECM) and of non-transformed cells (designated here as stromal cells), promote cancer cell survival and drug resistance. Many of the mechanisms involved are known and are either contact-dependent or contact-independent. Contact between tumor cells and the ECM or stromal cells as well as the production of soluble factors and microvesicles all contribute. The bone marrow plays a special role in environment-mediated drug resistance as it is not only a sanctuary protecting tumor cells from cytotoxic drugs, but also a source of many stromal cells that colonize primary tumors and contribute to the pre-metastatic niche. As our understanding of the mechanisms by which the tumor microenvironment promotes therapeutic resistance progresses, clinical trials testing agents that disrupt the interaction between tumor cells and the stroma have been initiated. This new avenue of therapy is promising.