Scientists may have developed a therapeutic approach to reverse cancer

New Indian Express

07-07-2025

How BENEIN works
BENEIN, a sophisticated computational model, is an artificial intelligence (AI) guided methodology that analyses gene expression at the single-cell level to map the complex regulatory networks that govern cell behaviour. The tool has been developed to uncover how genes cooperate within a cell and determine its identity - whether it remains cancerous or transforms into a healthy one.
Put simply, BENEIN works by treating each gene as a digital switch that is either turned on or off, and builds a logical map, called a Boolean gene regulatory network (GRN), to understand how these genes influence each other in the process of cellular differentiation (A process by which an immature cell develops into a specialised cell type with a distinct structure and function).
Using data derived from single-cell RNA sequencing, BENEIN analyses both exonic (mature) and intronic (immature) RNA fragments in each cell to determine the cell's status before and after genetic transitions. It can identify which genes are active at different stages of cell development or disease progression. The new approach reprogrammes cells, effectively turning back the cellular clock to their original function rather than destroying cancerous cells.
Once the gene network is mapped, BENEIN applies its network control theory to pinpoint a set of master regulators, whose regulation leads to the desired cellular differentiation. In the case of colorectal cancer cells, as the study mentioned, BENEIN identified a combination of three such master regulators - MYB, HDAC2 and FOXA2 - which play a critical role in blocking enterocyte differentiation, preventing cancer cells from maturing into normal intestinal cells.
When the researchers inactivated the three specific regulators (genes) in human colorectal cancer cells in the lab experiments, they observed a striking transformation - the cells slowed their growth, lost their aggressive behaviour, and began to resemble healthy intestinal cells. The team tested the approach in xenograft mouse models to validate these findings.
The mice injected with the reprogrammed cancer cells developed significantly smaller tumours than those given untreated cancer cells. Subsequently, the analysis of gene activity revealed that the reprogrammed cells closely resembled normal colon tissue, confirming that the therapy had effectively restored healthier cell behaviour.
'BENEIN was developed to systematically investigate the intestinal differentiation process through Boolean GRN analysis and identify the master regulators required for differentiation into enterocytes. Since single-cell transcriptomic data of differentiation trajectories of many other human tissues are becoming more available, BENEIN can be further utilised to identify master regulators of pan-tissue differentiation as well as reversion of pan-cancer cells,' the study stated.
A million hopes
As the treatment landscape of cancer keeps evolving, so does the understanding of the disease. Cancer, more than a disease, can be considered as a spectrum of cellular differentiation disorder. For a long time, there has been a great amount of research in the process or the events that aid the growth and development of cancer cells, popularly known as the hallmarks of cancer. The hallmarks are considered as the common features that all cancer cells are supposed to possess.
Apart from the core hallmarks of cancer, some other factors, called enabling characteristics, help cancer cells maintain sustained growth. One of the four enabling characteristics is unlocking phenotypic plasticity - the ability of cancer cells to alter their characteristics (phenotypes) in response to environmental changes, without undergoing genetic mutations.
Dr Sachin Sekhar Biswal, medical oncologist at Manipal Hospitals, Bhubaneswar said these cell alteration events leading to cancer are linked to acute promyelocytic leukemia, breast cancer, colorectal cancer, and hepatocellular cancer. 'The KAIST scientists have developed a new approach for treating colon cancer by reprogramming cancerous cells to resemble normal cells. This method has the potential to transform cancer treatment and give millions of people hope. However, this original research translating into clinical practice will need further research and several phases of successful human trials. But looking at the fundamentals of cancer and its development, this seems promising,' he said.
Dr Mukurdipi Ray, a senior surgical oncologist at AIIMS-Delhi, said the concept of controlling cellular differentiation is a promising area of research in cancer therapy. 'The study has shown that certain compounds can induce differentiation in specific types of cancer cells, leading to reduced tumour growth and improved outcomes. Since cancer is a heterogeneous disease and relapse is a major concern along with side effects and toxicity of treatments, controlling cellular differentiation trajectories for cancer therapy holds promise, but requires further research to overcome challenges and realise its full potential,' he observed.
The emerging approach mainly focuses on understanding the specific gene networks within each tumour and using targeted methods to reprogram malignant cells to stop growing. Such personalised reprogramming could significantly reduce relapse and resistance, while minimising side effects. As the reversion therapy doesn't kill cells but gently guides them toward normalcy, it may better preserve immune function and reduce toxicity. One of the most exciting aspects of this approach is that it doesn't depend on irreversible gene edits.
Dr Sai Vivek V, consultant (medical oncology and haemato oncology) at Aster Whitefield Hospital, Bengaluru said this new model is a very futuristic way of approaching cancer. 'Theoretically, this could become a great modality of cancer treatment in the future. We hope they will be able to start clinical trials on humans soon and isolate the cells, which is the most difficult part. If successfully translated to clinical practice, it might offer a more targeted and less toxic alternative to current treatment options,' he said.
India to benefit most
With the number of new cancer cases projected to rise from 1.46 million in 2022 to 2.5 million by 2030 in India, the implications of this study are profound. This growing trend is accompanied by troubling signs of late detection, poor survival outcomes, and an escalating economic burden on families and the healthcare system.
Statistically, nearly one in every nine Indians is expected to develop cancer during their lifetime. Lung cancer continues to be the most common cancer among Indian men, while breast cancer leads among women. In children, lymphoid leukaemia, followed by brain and central nervous system tumours are the predominant cancer types reported across both sexes.
Despite the growing burden, early detection remains a major challenge. Only about 29% of cancer cases in the country are diagnosed in early stages, with just 15% of breast and lung cancer cases and 33% of cervical cancers detected in stages 1 and 2. India has emerged as the oral cancer capital of the world with an alarming 90% of oral cancer cases being linked to smokeless tobacco products such as gutka and paan masala.
The country reported between 8-9 lakh cancer-related deaths a year, placing cancer among the top five causes of death over the past decade. The implications of this new discovery are particularly relevant to India, where the cancer burden is rapidly rising. According to the Indian Council of Medical Research (ICMR), colorectal cancer is among the top five most prevalent cancers in the country, especially in urban populations.
Although newer therapies like immunotherapy and precision medicine are gaining ground, they remain prohibitively expensive for most Indian patients. Dr Dillip Kumar Parida, senior radiation oncologist and medical superintendent at AIIMS Bhubaneswar, said he is very optimistic about the KAIST model that could be very beneficial for early stage cancers.
'Our hospitals see a huge load of late-stage patients. If we can identify master regulators early using tools like BENEIN, we may be able to prevent cancers from progressing. Once we have access to local transcriptomic databases, this framework can be used for tailor-made therapies for Indian sub-populations. This gene-reversion strategy, once clinically proved and refined, could offer a more cost-effective and less toxic alternative,' Dr Parida added.