Cancer cells converted into healthy cells with new approach

Inhibition of genes that regulate cell differentiation reverts colorectal cancer cells back into healthy cells.

Traditional cancer treatments aim to eliminate cancer cells, but this has limitations. Cancer cells can develop resistance to these therapies, leading to recurrence. Additionally, these treatments often harm healthy cells, causing severe side effects. To address these challenges, researchers at the Korea Advanced Institute of Science and Technology (KAIST) employed cancer reversion as an alternative approach. Cancer cells are often 'undifferentiated', meaning they lose the specialised features of normal cells. Cancer reversion restores these cells to their differentiated, non-malignant state.

'The fact that cancer cells can be converted back to normal cells is an astonishing phenomenon,' said Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering at KAIST, and lead author of this study. He continued, 'This study proves that such reversion can be systematically induced.'

This research, published in Advanced Science, aimed to revert colorectal cancer cells into healthy cells. First, the group developed BENEIN, a computational tool to identify genes responsible for cancer cell 'undifferentiation'. BENEIN identified a gene network crucial for this process by analysing data from 4252 healthy colon cells undergoing differentiation. With this information, the team pinpointed three master genes essential for colon cell differentiation: MYB, HDAC2 and FOXA2. Removing these genes successfully reverted colorectal cancer cells into healthy cells, both in cell and mouse models.

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

Cancer cell reversion has been explored in the past, for example in leukaemia and breast cancer. However, identifying genes to target undifferentiation has traditionally relied on trial and error. BENEIN offers a systematic, data-driven approach to identify these genes, moving beyond reliance on chance discoveries.

In this study, BENEIN was applied to identify master regulators that can revert colorectal cancer cells, however the researchers believe it to be a versatile tool that extends beyond colon cancer, with the potential to be applied to any type of cell.

To evaluate BENEIN's applicability to other tissues, the researchers applied it to mouse hippocampus data. In particular, the group focused on the differentiation of granular cells in the brain. Once again, BENEIN successfully generated a network of the genes involved in this process. This demonstrates BENEIN's capability to identify targets for controlling cell differentiation in a variety of biological contexts.

The authors conclude, 'BENEIN provides a systemic approach to identify master regulators of cell differentiation and reprogramming, and opens a novel route to further investigate the role of such regulators for mechanism-based therapeutic strategies.'