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A South Korean group of scientists, led by professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering are working out the details of a new technology called Digital Twin Modeling to revert colon cancer cells into normal colon cells without killing them (KAIST PR office, 2024). With the knowledge that normal colon cells will follow a trajectory of differentiation into a cancer cell, the team created a digitial twin of the gene network associated with the differentiation of normal colon cells into cancer cells. Through simulation analysis, the team was able to identify master molecular switches in the genes that signal a cell to turn into a cancer cell. Through a complex analysis of these on/off switches within the gene of the cell, the scientists were able to apply these switches to the cancer cell and found that the cell will revert back into a normal colon cell. The technology allows the scientists to systematically identify the key regulatory factors within the cell's genes that induce the cell to convert to a cancerous cell and vice versa. The digital twin technology provides a systematic approach rather than relying on serendipitous discovery.

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Despite the development of numerous cancer treatment technologies, the common goal of current cancer therapies is to eliminate cancer cells. This approach, however, faces fundamental limitations, including cancer cells developing resistance and returning, as well as severe side effects from the destruction of healthy cells.

KAIST (represented by President Kwang Hyung Lee) announced on the 20th of December that a research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering has 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. When these switches were applied to colon cancer cells, 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.

Professor Kwang-Hyun Cho remarked, "The fact that cancer cells can be converted back to normal cells is an astonishing phenomenon. This study proves that such reversion can be systematically induced."

He further emphasized, "This research introduces the novel concept of reversible cancer therapy by reverting cancer cells to normal cells. It also develops foundational technology for identifying targets for cancer reversion through the systematic analysis of normal cell differentiation trajectories."

This research included contributions from Jeong-Ryeol Gong, Chun-Kyung Lee, Hoon-Min Kim, Juhee Kim, and Jaeog Jeon, and was published in the online edition of the international journal Advanced Science by Wiley on December 11. (Title: "Control of Cellular Differentiation Trajectories for Cancer Reversion") DOI: https://doi.org/10.1002/advs.202402132

The study was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-Career Researcher Program and Basic Research Laboratory Program. The research findings have been transferred to BioRevert Inc., where they will be used for the development of practical cancer reversion therapies.

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The major benefit of such a discovery hinges on the fact that cancer treatment today is geared towards destruction of the cancer cells. However, with these treatments such as chemotherapy and radiation, healthy body cells are also damaged or killed. Reprogramming cells back into normal body cells could potentially eliminate the systemic side effects and overall toxicity associated with current treatments (Science Daily, 2024).

Additionally, there is evidence that reprogramming cells back into normal body cells would reduce the risk of recurrence because the reprogramming is thought to diminish the malignancy and aggressive behavior of the cells (Science Daily, 2024).

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Perhaps, the most obvious drawback to the current research of digital twin modeling is that it is still in the preclinical phase; this means that results have only been validated using cell cultures and animal models (Science Daily, 2024). More research is needed to determine the effectiveness for human therapy.

There also remains the possibility that cells can revert back to cancer cells, a term called incomplete programming (KAIST, 2024).

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When weighing the pros and cons of the digital twin technology with the promise of a cancer treatment that can revert cancer cells back to normal body cells without the adverse side effects commonly seen in current treatments, I remain optimistic and certainly in favor of ongoing research. Instead of cell destruction, reprogramming cancer cells back to normal body cells offers a transformative approach to cancer treatment that could relieve suffering, improve quality of life, and provide an ethically centered treatment for cancer.

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Korean Researchers Discover Cancer’s 'Undo' Button