KAIST’s Breakthrough: Reprogramming Colon Cancer Cells to Behave Normally

In the long and often punishing battle against cancer, modern medicine has relied heavily on eradication: cut, burn, poison — remove the disease before it removes the patient. While effective in many cases, this strategy has never been without consequences. It often sacrifices healthy cells alongside malignant ones and carries the looming shadow of recurrence. Yet, in a remarkable development from South Korea’s KAIST (Korea Advanced Institute of Science and Technology), a new chapter may be unfolding — one that doesn’t seek to kill cancer, but to retrain it.

Led by Professor Kwang-Hyun Cho, researchers at KAIST have introduced an entirely new paradigm: reprogramming cancer cells. Their work on colon cancer suggests that, under the right conditions, these malignant cells can be coaxed back toward their original, healthy identities. Rather than destruction, the goal becomes rehabilitation — a fundamental rethinking of what cancer therapy can be.

This discovery reframes the question at the heart of oncology. If cancer is, in part, the result of misdirected or corrupted cellular programming, might we not destroy the cell but repair its code?

Fun Fact: The term “cancer” comes from the Latin for crab, referencing the way tumours appear to claw into tissues — but this new research hints that even the crab might learn to retreat.

Understanding the Biology: Why Cancer Reprogramming Is Possible

To appreciate KAIST’s innovation, one must first consider how cancer begins. At its core, cancer arises from dedifferentiation — the loss of a cell’s specialisation. Healthy cells, like those lining the colon, have distinct roles. But when they begin to lose that identity, shedding their function and instead focusing on survival and replication, they transform into cancer cells.

Traditional therapies — chemotherapy, radiotherapy, and even immunotherapy — have all focused on finding and eliminating these rogue cells. Yet this approach is inherently destructive. Rapidly dividing cells, like those in hair follicles or bone marrow, are often caught in the crossfire. And worse still, cancer has a way of adapting. Resistance to treatment, and the risk of relapse, remains a constant threat.

This is where reprogramming offers new promise. The premise is elegant in its simplicity: cancerous cells are not evil — they’re confused. If we can identify the molecular instructions they’ve lost, we might guide them back to their original, healthy pathways. The result? A cell that no longer behaves like a tumour.

The KAIST Breakthrough: Targeting the Identity of Colon Cancer

Professor Cho’s team has not only proposed this idea — they’ve demonstrated it, with precision. Their work hinges on two computational platforms: BENEIN and REVERT, both designed to map and manipulate the gene networks that determine a cell’s identity.

Boolean Network Inference and Control

The BENEIN framework, central to a 2025 study published in Advanced Science, analyses single-cell data to pinpoint master regulatory genes — the molecular switches that decide whether a cell behaves normally or like a cancer. Applied to colon cancer, BENEIN identified three key targets: MYB, HDAC2, and FOXA2. These genes are known contributors to cancer growth and abnormal behaviour.

Using laboratory-grown colon cancer cell lines — HT-29, CACO-2, and HCT-116 — the team simultaneously silenced all three genes. The results were striking: the cells stopped proliferating like tumours and began expressing markers typical of healthy colon cells.

But this wasn’t just a petri-dish miracle. In animal models, tumours with these three genes suppressed grew significantly smaller, showing the potential for in-body application.

Intervening at the Edge of Tumorigenesis

Where BENEIN looks at reprogramming existing cancer, REVERT targets cells teetering on the edge of malignancy — the “critical transition” phase where normal cells are beginning to turn cancerous. In this research, another gene, USP7, was identified as a crucial switch. Blocking USP7 helped push pre-cancerous colon cells back toward normalcy, preventing full-blown transformation.

Together, BENEIN and REVERT form a complementary toolkit: one reversing cancer, the other halting it before it begins.

Digital Twins and Network Control

What enables such targeted interventions is KAIST’s use of digital twins — virtual models of gene regulatory networks based on data from single-cell RNA sequencing. Think of these as dynamic, living maps that show how each gene interacts with others to determine cell behaviour.

Using Boolean logic — where genes are treated as either “on” or “off” — the BENEIN system can simulate how thousands of genes behave under different conditions. By virtually silencing or activating specific genes, researchers can test countless combinations without ever touching a test tube.

This level of precision modelling allows researchers to avoid trial-and-error, pinpointing interventions with surgical accuracy. These frameworks represent a leap forward in personalised medicine, where treatments can be tailored not just to a cancer type, but to the specific genetic logic of an individual’s tumour.

A New Therapeutic Philosophy

What distinguishes KAIST’s reprogramming approach is not only its method but its underlying philosophy. Most cancer treatments today aim to kill. Whether through chemotherapy’s toxic assaults or radiotherapy’s high-energy bombardment, the goal is simple: destroy the malignant cell before it spreads.

But this approach, while sometimes effective, often carries devastating side effects. Immune therapies, meanwhile, empower the body to fight back — but can also misfire, attacking healthy tissues.

Reprogramming offers a third way: rather than destroy, it seeks to restore. By modulating the regulatory genes that control identity and behaviour, cancer cells can be nudged away from malignancy. This method may reduce harm to healthy tissue, avoid triggering immune overreactions, and potentially yield more stable, longer-lasting remissions.

Here’s how the reprogramming approach compares:

This shift — from warfare to biological rehabilitation — marks a potential turning point in cancer medicine. If successful, it may mean that future patients spend less time enduring treatments, and more time recovering — not just surviving, but thriving.

The Promise of Gentler, More Lasting Cancer Care

If this reprogramming strategy proves effective in humans, its most immediate benefit would be a drastic reduction in side effects. Chemotherapy and radiotherapy damage healthy, fast-dividing cells — leading to fatigue, nausea, immune suppression, and a severely reduced quality of life. Reprogramming therapies, by contrast, don’t aim to kill, but to correct. This shift in mechanism could result in far fewer adverse effects, making the treatment journey more humane.

Another major advantage lies in the potential to overcome drug resistance. Conventional therapies often become less effective over time, as cancer cells evolve to evade them. But if a tumour cell is reverted to a normal phenotype, its malignant features disappear altogether — side-stepping the very mechanisms that cause resistance. This could make relapses less likely and responses more durable.

Perhaps most compelling of all is the possibility of true cellular repair. Reprogrammed cells don’t just stop growing — they may resume the healthy functions of the tissue they once damaged. In the case of colon cancer, that means maintaining the intestinal lining and preventing inflammation. In this vision, cancer therapy doesn’t just neutralise disease; it contributes to functional restoration.

The Visionary Professor Cho and KAIST’s Research Legacy

At the centre of this scientific leap stands Professor Kwang-Hyun Cho, an internationally recognised systems biologist. Based in KAIST’s Department of Bio and Brain Engineering, Professor Cho also directs the Laboratory for Systems Biology and Bio-Inspired Engineering — a hub where biology, engineering, and computation converge.

Cho’s lab has long pursued the goal of cancer reversion, and its achievements extend beyond colon cancer:

1. In 2020, the team showed early evidence that colon cancer cells could revert to normal colon-like cells.
2. In 2022, they reprogrammed breast cancer cells to become hormone-sensitive, increasing treatment responsiveness.
3. In 2023, they removed metastatic traits from lung cancer cells.
4. In 2025, they identified a key inhibitor of immunotherapy effectiveness in lung cancer — suggesting reversion could even enhance existing treatments.

The laboratory’s methodical progress shows not just intellectual ambition, but a serious commitment to therapeutic translation. Their consistent use of cutting-edge technologies like digital twins and Boolean modelling demonstrates a clear research arc: turning complex biology into clinically actionable insight.

Toward Clinical Application

While still in the preclinical stage, this research has already cleared several vital hurdles. The team has validated their reprogramming approach in:

1. Human colon cancer cell lines (HT-29, CACO-2, HCT-116)
2. Patient-derived organoids, which mimic the 3D structure of real tumours
3. Animal models, where cancerous cells treated with reprogramming protocols formed significantly smaller tumours

These in vivo results are especially encouraging, as they suggest the technique holds up under the biological complexity of a living system.

Even more promising is the formation of BioRevert Inc., a biotechnology company co-founded by Professor Cho. The company has acquired the rights to the KAIST findings and is actively developing drug delivery platforms to bring reprogramming therapies to market. Its pipeline already includes early-stage programmes targeting colon, liver, and lung cancers.

This move from academia to industry shows that KAIST’s researchers are not content to publish papers — they are actively engineering pathways to patient care.

Challenges on the Horizon for Real-World Impact

Despite its promise, this reprogramming approach must still clear substantial obstacles.

1. Stability: One major question is whether the reverted cells will remain stable over time, or if they might relapse into malignancy. Cancer is highly adaptable, and partial reprogramming may leave behind molecular “memories” of disease.
2. Delivery: Silencing multiple genes in human tumours requires advanced delivery tools. shRNA or siRNA-based therapies, while effective in lab settings, face hurdles like immune clearance, off-target effects, and inefficient uptake in solid tumours.
3. Specificity: Genes like MYB, HDAC2, and FOXA2 aren’t exclusive to cancer. They play roles in normal cells too. Ensuring that therapies selectively target tumour cells will be essential to avoid unintended harm.
4. Tumour Heterogeneity: Not all cancer cells within a tumour behave identically. Some may respond to reprogramming, others may resist it. Tackling this biological diversity is a known challenge across all forms of precision oncology.
5. Regulatory Approval: Any new therapeutic must undergo rigorous human trials. The journey from mouse models to regulatory green light is typically measured in years and requires vast resources.

Yet none of these challenges is insurmountable. Indeed, many parallel efforts in gene therapy, epigenetic editing, and targeted delivery are likely to benefit this approach. What matters is sustained investment and collaborative development.

Conclusion: A Hopeful Future for Oncology

The cancer research emerging from KAIST and Professor Cho’s lab may mark the beginning of a new therapeutic era. By demonstrating that colon cancer cells can be systematically reverted to a normal-like state, the team has done more than develop a clever technique — they’ve introduced a new mindset.

This approach doesn’t seek to destroy cancer at any cost. Instead, it aims to understand its logic, rewire its circuits, and restore its original identity. It replaces bombs with blueprints, chemo with code.

Whether this will become the standard of care in ten years or remain a niche solution will depend on rigorous testing, clinical success, and translational support. But for now, the signs are promising. From digital twins to real-world xenografts, the science is sound — and the vision is bold.

For patients, clinicians, and researchers alike, the message is clear: the war on cancer may not be won through destruction, but through understanding, modelling, and re-education.