Current status in cancer cell reprogramming and its clinical implications

Kenan Izgi, Halit Canatan, Banu Iskender

The technology of reprogramming a terminally differentiated cell to an embryonic-like state uncovered the possibility of reprogramming a malignant cell back to a more manageable stem cell-like state. Since the current cancer models suffer from reflecting heterogeneous tumour structure and limited to express the late-stage markers, the induced pluripotent stem cell (iPSC) technology could provide an alternative model to recapitulate the early stages of cancer. Generation of iPSCs from cancer cells could offer a tool for understanding the mechanisms of tumour initiation-progression in vitro, a platform for studying tumour heterogeneity and origin of cancer stem cells and a source for cancer type-specific drug discovery studies. In this review, we discussed the recent findings in reprogramming cancer cells with a special emphasis on similarities between cancer cells and pluripotent cells. We presented the basis of challenges in cancer cell reprogramming including the current problems in reprogramming, cancer-specific epigenetic state and chromosomal aberrations. Cancer epigenetics represent the major hurdle before the prospective use of cancer iPSCs as a model system and for biomarker research. When the reprogramming process is optimised for cancer cell types, it might serve for two purposes: identification of the specific epigenetic state of cancer as well as reversion of the malignant phenotype to a potentially malignant but manageable state. Reprogramming cancer cells would serve for our understanding of cancer-specific epigenome and elucidation of overlapping mechanisms shared by cancer-initiating cells and pluripotent cells.