In a significant leap forward in the battle against cancer, a team of researchers from Monash University, in partnership with Harvard University, has unveiled a revolutionary method to permanently disable genes that drive cancer growth. This pioneering work, published in the highly respected journal Nature Cell Biology, opens the door to novel cancer treatments that promise not only improved efficacy but also drastically reduced treatment durations and fewer debilitating side effects. This breakthrough could transform the patient experience and outcomes in oncology.
At the heart of this discovery lies epigenetic therapy, an innovative approach that does not target the cancer cells directly but the molecular mechanisms that regulate gene expression. Epigenetics refers to the study of heritable changes in gene function that do not involve alterations of the underlying DNA sequence. By influencing these regulatory controls—specifically the switching on or off of genes—scientists aim to correct the abnormal gene expression patterns induced by cancer-causing mutations. Such interventions can potentially reset the malignantly altered genetic machinery of cancer cells back to a healthy state.
The team has focused their research on aggressive acute leukemia subtypes, which are notoriously difficult to treat and often resistant to conventional therapies. In this form of leukemia, a specific genetic anomaly disrupts the cell’s natural gene-regulatory systems, leading to the persistent activation of oncogenes, the genes responsible for promoting cancer cell survival and proliferation. While existing drugs targeting the epigenetic modulators involved in this process have shown promise, the underlying mechanisms governing their effectiveness remained elusive until now.
Led by Senior Research Fellow Dr. Omer Gilan at Monash University’s School of Translational Medicine and the Australian Centre for Blood Diseases, the study elucidates how targeting two particular epigenetic proteins—Menin and DOT1L—can permanently silence the runaway cancer-driving genes in leukemia cells. This permanent gene ‘switching off’ fundamentally undercuts the cancer cells’ ability to continue thriving, introducing a new paradigm in the way epigenetic therapies may be applied clinically.
Dr. Gilan emphasizes that this discovery exploits a critical vulnerability within cancer cells, a weakness that previous therapeutic approaches failed to fully leverage. “This might represent a new route to incapacitate the genetic drivers of leukemia,” he notes. Significantly, the implications extend beyond experimental settings, offering clinicians a powerful tool to improve patient responses to treatment while minimizing the adverse effects that frequently compromise quality of life during therapy.
Central to this therapeutic advance is the concept of ‘transcriptional memory,’ a phenomenon maintained by the epigenetic factor DOT1L within leukemia cells. Daniel Neville, a PhD candidate at Monash and the paper’s lead author, explains that the drugs targeting Menin effectively erase the transcriptional memory DOT1L provides. This erasure allows the treatment to exert a lethal effect on the cancer cells that endures well beyond the treatment window itself, ensuring continued suppression of oncogenic activity.
The persistent gene silencing achieved by targeting these epigenetic proteins means shorter courses of therapy may suffice, potentially reducing toxic side effects and improving the tolerability of higher or combination doses. This is a particularly promising prospect as it raises the possibility of integrating novel epigenetic treatments alongside conventional or emerging therapies, amplifying their collective impact against cancer.
Epigenetic therapy, previously considered a promising but challenging field, now appears poised to secure a firm place in the front line of cancer treatment strategies. This research offers compelling evidence that permanent modulation of gene expression in cancer cells is achievable, a finding that may revolutionize therapeutic protocols not only for leukemia but potentially across various malignancies characterized by aberrant epigenetic landscapes.
A next critical step in translating these findings to clinical practice is already underway, with Monash University and The Alfred Hospital preparing to initiate clinical trials later this year. These trials will evaluate the safety and efficacy of Menin inhibitors in patients, scrutinizing the therapeutic impact of the new approach as well as its real-world side effect profile.
Associate Professor Shaun Fleming, a clinical hematologist and head of the myeloid disease program at The Alfred, underscores the excitement surrounding this advancement. With ongoing and future clinical studies involving Menin inhibitors, understanding their mechanisms of action will facilitate more effective and safer applications, enabling tailored treatment regimens for patients battling acute leukemia and potentially other cancers.
This breakthrough not only underlines the crucial role of epigenetic research in oncology but also showcases the power of interdisciplinary collaboration between leading institutions globally. The discovery propels the scientific community closer to therapies that strike at the very core of cancer’s genetic aberrations with precision and persistence.
As the scientific and medical communities await the results from upcoming clinical evaluations, the prospects for patients suffering from aggressive leukemias look brighter. This novel strategy may dramatically reshape cancer treatment paradigms in the coming years, reducing the human toll of cancer and offering hope for more durable remissions.
Subject of Research: Epigenetic regulation of gene expression in leukemia, targeting Menin and DOT1L proteins to permanently silence oncogenes.
Article Title: DOT1L provides transcriptional memory through PRC1.1 antagonism
News Publication Date: February 3, 2026
Web References: 10.1038/s41556-025-01859-8
Keywords: Epigenetics, cancer treatment, acute leukemia, Menin inhibitors, DOT1L, transcriptional memory, gene expression, epigenetic therapy, oncology, gene silencing
Tags: acute leukemia treatment advancementsepigenetic therapy breakthroughsgene expression regulation in cancerheritable gene function changesimproving patient outcomes in cancer treatmentinnovative cancer treatmentsmolecular mechanisms in oncologyMonash University cancer researchpermanently disabling cancer genesreducing cancer treatment side effectsreversing cancer-causing mutationstargeted cancer therapies
