Tumor reversion history started in the early 1960s with the flat revertant cells when researchers used the NIH3T3 cells to assay the transforming potential of oncoviruses and oncogenes. Robert Pollack, later in 1968, made the observation that some of the cells infected with SV40 or polyoma viruses no longer showed the typical oncogenic phenotype, but instead, acquired a flat morphology (Pollack et al., 1968). These cells had also lost their oncogenic potential and were therefore named "flat revertants".
New approaches, using different biological systems led to the identification of more than 300 genes, implicated in the tumor reversion process (Telerman et al., 2009). Targeting genes of tumor reversion to suppress the malignant phenotype led to the identification of a series of drugs able to inhibit intra-cellular levels of TCTP, a key gene in tumor reversion.