Turning Cancer Cells Back into 'Normal Cells'

Development of Fundamental Technology for Cancer Cell Normalization
Opening a New Chapter in Anticancer Therapy

When the expression of SETDB1 was suppressed in colorectal cancer organoids (3D cultured organ-like structures) derived from a colorectal cancer patient, the morphology of normal colorectal organoids was restored.

[Asia Economy Reporter Junho Hwang] Domestic researchers have succeeded in developing a fundamental technology that reverts cancer cells back to normal cells. Depending on follow-up studies, a new chapter in anticancer treatment called 'normalization of cancer cells' is likely to open.

KAIST announced on the 9th that Professor Kwanghyun Cho's research team in the Department of Bio and Brain Engineering developed an initial fundamental technology that reverts colon cancer cells to typical normal cells.

Discovery of Key Factors That Revert Cancer Cells to Normal Cells

The research team analyzed the gene regulatory networks of colon cancer cells and normal colon cells to identify key factors necessary for converting cancer cells into normal cells. The main players are core transcription factors such as CDX2, ELF3, HNF4G, PPARG, VDR, and the epigenetic regulator SETDB1, which suppresses their activity.

In particular, they found that SETDB1 inhibits the core transcription factors of normal cells, thereby blocking the conversion of cancer cells into normal cells. They also confirmed that when SETDB1 was suppressed in colon cancer cells, the cells stopped dividing and restored the gene expression patterns of normal colon cells. Through collaborative research with Seoul Samsung Hospital, the team discovered that suppressing SETDB1 expression in colon cancer organoids (3D cultured organ-like structures) caused them to revert to a form similar to normal cells.

From 'Cancer Cell Death' to 'Cancer Cell Normalization': A New Chapter in Anticancer Treatment

This research outcome is expected to serve as a foundation that can open a new chapter in anticancer treatment. Although there have been new therapeutic strategies aimed at converting cancer cells into normal cells, the underlying principles and control technologies have not been specifically studied.

Currently, no small molecule compounds that can inhibit SETDB1 have been developed. However, if new drug development and preclinical trials proceed in the future, a new paradigm of anticancer treatment based on 'normalization of cancer cells' is expected to be realized. Until now, cancer treatments have focused mainly on killing cancer cells, which causes significant suffering for patients.

Professor Cho stated, "Cancer has long been considered irreversible because it results from accumulated genetic mutations, but we have shown the possibility of reversing it," adding, "This research opens the dawn of a new anticancer treatment that manages cancer as a chronic disease like diabetes or hypertension, allowing patients to maintain their quality of life."

This research was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-career Researcher Support Program, the Bio-Medical Technology Development Program, and the KAIST Grand Challenge 30 project.

The research results were published as the cover paper in the June 2 issue of the international journal Molecular Cancer Research, published by the American Association for Cancer Research (AACR).