Selective evolutionary pressure from the tissue microenvironment drives tumor progression

Cells grow within defined environmental niches and are subject to microenvironmental control. Outside of their niche, the environment is hostile, the normal cells lack appropriate survival signals which leads to anoikis. During tumor development and progression, malignant cells must escape the local tissue control and resist anoikis. The inherent genetic instability of tumor cells makes their phenotype very plastic, which changes under continuous environmental selection pressure. In this way the microenvironment drives the somatic evolution of the tumor. In the current review, we assess how this environmental selection pressure fits into the classical scheme of tumor progression.