Lung adenocarcinoma (LUAD), a leading cause of cancer-related deaths, may have met its match in the form of a tiny chemical tag known as m6A methylation. Recent research from UHN’s Princess Margaret Cancer Centre reveals that this small modification to RNA plays a critical role in driving LUAD progression and metastasis.
The study identifies m6A modifications in two key genes—BLVRA and EML4—as significant indicators of poor prognosis. Patients with high levels of m6A in the BLVRA gene face a greater risk of cancer-related death. Meanwhile, increased modification of the EML4 gene has been shown to propel tumour metastasis, the process by which cancer spreads to other parts of the body.
What makes this discovery particularly exciting is the potential for targeted treatments. By using a small-molecule inhibitor to reduce m6A modifications in the EML4 gene, researchers successfully decreased tumour metastasis in experimental models. This points to a new therapeutic strategy aimed at halting the spread of LUAD at its molecular roots.
As LUAD continues challenging even the most advanced treatments, these findings offer a promising new approach. By focusing on m6A methylation, researchers are not only enhancing our understanding of lung cancer but also laying the groundwork for future therapies that could save lives. This research represents a crucial step toward more effective treatment options for patients with this aggressive disease.
This study is funded by the Canada Foundation for Innovation (CFI), Natural Sciences and Engineering Research Council of Canada (NSERC), Canadian Cancer Society (CCS), Canadian Institutes of Health Research (CIHR), Terry Fox Research Institute (TFRI), and The Princess Margaret Cancer Foundation (PMCF).
Dr. Housheng (Hansen) He is a Senior Scientist at UHN's Princess Margaret Cancer Centre and an Associate Professor in the Department of Medical Biophysics at the University of Toronto.
Dr. Ming-Sound Tsao is a Senior Scientist at UHN’s Princess Margaret Cancer Centre and a Professor in the Departments of Medical Biophysics and Laboratory Medicine and Pathobiology at the University of Toronto.
Wang S, Zeng Y, Zhu L, Zhang M, Zhou L, Yang W, Luo W, Wang L, Liu Y, Zhu H, Xu X, Su P, Zhang X, Ahmed M, Chen W, Chen M, Chen S, Mykhaylo S, Xie Z, Guan J, Zhang W, Khan AA, Sakashita S, Liu N, Pham NA, Boutros PC, Ke Z, Moran MF, Cai Z, Cheng C, Yu J, Tsao MS, He HH. The N6-methyladenosine Epitranscriptomic Landscape of Lung Adenocarcinoma. Cancer Discovery. 2024 August CD-23-1212. https://doi.org/10.1158/2159-8290.CD-23-1212. Epub 2024 August 13.