A Korean research team has proposed a new cancer treatment strategy based on cancer cell reprogramming therapy.
The National Cancer Center (NCC) announced Tuesday that a research team led by Professor Shin Dong-kwan of the Bioinformatics Research Department at NCC and Professor Cho Kwang-hyun of the Department of Bio and Brain Engineering at KAIST has developed “REVERT,” a method capable of reverting cancer cells to a state closer to normal.
REVERT is a foundational technology that identifies reversion switches based on systems biology.
Conventional cancer treatments, such as chemotherapy or radiation therapy, have focused on killing cancer cells. Additionally, reprogramming therapy, which reverses cancer cells into normal cells, has been utilized to reduce side effects and enable more effective treatment. However, it has been difficult to clearly identify which genes need to be regulated to reverse the cells.
Therefore, the research team analyzed single-cell gene data to capture the Critical Transition state—the boundary point between normal and cancer cells. This state occurs just before a cell fully transitions to cancer and can be reversed to normal with external intervention.
Based on this, the team mapped how genes connect and influence each other within cells and conducted thousands of virtual experiments. They discovered that the genes YY1 (Yin Yang 1) and MYC act as key switches in cell fate conversion. These genes regulate cell growth and division, and simultaneously inhibiting them significantly increased the likelihood of cells regaining normal properties.
Furthermore, by tracing the points jointly regulated by these genes, the team newly identified USP7 (Ubiquitin Specific Peptidase 7). Applying a USP7 inhibitor to patient-derived colorectal cancer organoids (mini-organs) significantly reduced tumor growth and partially restored normal colon tissue characteristics. This demonstrates that the REVERT prediction was validated in actual experiments, showing cancer cells can revert to a normal state.
However, the research team emphasized that this study is at the basic research stage involving cells and organoids, and clinical validation is required before it can be applied to actual patient treatment.
“If existing cancer treatments were like a hammer smashing the machine that is the cancer cell, REVERT is like a precision tool that understands the machine's circuit diagram, finds the faulty switch, and turns it back on,” Professor Shin said. “It is highly significant in that it opens the possibility for a new treatment strategy.”
This research was supported by the National Cancer Center's Public Interest Cancer Research Project, the Ministry of Science and ICT's National Research Foundation Mid-Career Researcher Program and Basic Research Laboratory Program, and the Ministry of Health and Welfare's Korea Health Industry Development Institute Disease-Centered Translational Research Project.
The findings were published in the international journal Advanced Science under the title “Attractor Landscape Analysis Reveals a Reversion Switch in the Transition of Colorectal Tumorigenesis.”