Traditional cancer therapies aim to destroy tumor cells, often damaging nearby healthy tissue and triggering harsh side effects. Publishing their results in Advanced Science, the researchers outlined a method to steer cancer cells away from uncontrolled growth and back toward a differentiated, stable identity.
In a discovery that could rewrite the rules of cancer treatment, scientists in South Korea have reversed the malignant nature of cancer cells — without killing them. Instead of targeting tumors with radiation or chemotherapy, researchers reprogrammed the cells to behave like normal tissue. Their experimental method, tested on colorectal cancer, doesn’t destroy tumors — it redeems them.
Leading the work is Professor Kwang-Hyun Cho and his team at the Korea Advanced Institute of Science and Technology (KAIST), who used a powerful computational model called a digital twin to guide this cellular transformation.
Traditional cancer therapies aim to destroy tumor cells, often damaging nearby healthy tissue and triggering harsh side effects. Cho’s team took a different path. Publishing their results in Advanced Science, the researchers outlined a method to steer cancer cells away from uncontrolled growth and back toward a differentiated, stable identity.
At the heart of their method is a computational system called BENEIN (Boolean Network Inference and Control), which models how genes interact inside individual cells. By mapping these interactions, BENEIN identifies key genetic regulators that control whether a cell behaves malignantly or normally.
The study zeroed in on three such regulators — MYB, HDAC2, and FOXA2. “The simultaneous knockdown of MYB, HDAC2, and FOXA2 strongly induces differentiation into normal-like cells,” the researchers reported.
Using data from 4,252 intestinal cells, the team reconstructed a gene network with 522 components. Simulations predicted that turning off these three genes would halt cancer cell proliferation. The prediction held up in lab-grown colorectal cancer cell lines and in animal models.
In human cell lines HCT-116, HT-29, and CACO-2, the triple knockdown slowed cell growth more effectively than knocking down any single gene. When these treated cells were implanted into mice, the resulting tumors were significantly smaller in both size and weight than those from untreated controls.
Further analysis showed that treated cells expressed markers typical of healthy intestinal cells, such as KRT20 and VDR, while cancer-associated pathways like MYC and WNT were suppressed. The gene expression patterns also closely matched those of healthy tissue samples in The Cancer Genome Atlas.
Beyond cancer, the BENEIN framework proved effective in other systems. It accurately identified key regulators in mouse hippocampus development and T cell activation, outperforming existing tools like SCENIC and VIPER.
While challenges remain—such as adapting the method to various tissues and ensuring the long-term stability of reverted cells—the potential is profound. If refined and clinically applied, this technique could shift cancer treatment from destruction to reprogramming.
The study, Control of Cellular Differentiation Trajectories for Cancer Reversion, was published on December 11, 2024, in Advanced Science.
Source : Businesstoday
