Different experimental models reveal that malignant cancer cells can be induced to change their phenotype into a benign one. This phenotypic transformation, confirmed both in vitro and in vivo, currently is known as 'tumor reversion'. This evidence raises a radical question among current cancer models: Is cancer reversible? How do genetic and epigenetic alterations hierarchically relate? Understanding the mechanisms of 'tumor reversion' represents a key point in order to evolve the actual cancer models and develop new heuristic models that can possibly lead to drugs that target epigenetic mechanisms, for example epigenetic drugs. Even though evidence of tumor reversion dates back to the 1950s, this remains a completely new field of research recently re‑discovered thanks to the interest in cell reprogramming research, developmental biology and the increasing understanding of epigenetic mechanisms. In the current review, a comprehensive review of all the main experimental models on tumor reversion was presented.
Keywords: cancer phenotype; embryo development; morphogenesis; phenotypic reversion; philosophy of cancer; systems biology; tumor Microenvironment; tumor reversion.