Reprogramming Colon Cancer Cells into Normal Cells
A cell is just a state machine; control its gene expression, control over the production of proteins, implies control of its behavior and activity. Given sufficient knowledge and ability to make specific changes in gene expression, there is no such thing as an irreversible cell state - except in the case that nuclear DNA damage has removed the ability to express correct proteins, one would think. So while reversing cellular senescence is one thing, it is interesting to find that at least some cancerous cell types can be reverted to essentially normal cells. Is this a safe and useful approach to cancer therapy, or will it just create a sizable population of cells that retain the mutational damage that will predispose them to becoming cancerous again?
Researchers have developed a groundbreaking technology that can treat colon cancer by converting cancer cells into a state resembling normal colon cells without killing them, thus avoiding side effects. The research team focused on the observation that during the oncogenesis process, normal cells regress along their differentiation trajectory. Building on this insight, they developed a technology to create a digital twin of the gene network associated with the differentiation trajectory of normal cells.
Through simulation analysis, the team systematically identified master molecular switches that induce normal cell differentiation. Three genes, HDAC2, FOXA2, and MYB, were discovered as key control factors that induce differentiation of normal colon cells. When these three genes were knocked down the cancer cells reverted to a normal-like state, a result confirmed through molecular and cellular experiments as well as animal studies. This research demonstrates that cancer cell reversion can be systematically achieved by analyzing and utilizing the digital twin of the cancer cell gene network, rather than relying on serendipitous discoveries. The findings hold significant promise for developing reversible cancer therapies that can be applied to various types of cancer.
Link: https://news.kaist.ac.kr/newsen/html/news/?mode=V&mng_no=42710