Researchers at Cold Spring Harbor Laboratory (CSHL) have made significant strides in understanding the progression of triple-negative breast cancer (TNBC) by examining a long non-coding RNA known as MALAT1. Traditionally, cancer therapy targets focus on protein-coding genes that contribute to the disease. However, this innovative study reveals how tracking MALAT1 levels can provide critical insights into TNBC’s progression and potential treatment avenues.
In a unique study published in Molecular Therapy: Oncology, CSHL researchers monitored the levels of MALAT1 throughout the treatment journey of a 59-year-old woman diagnosed with stage 1 TNBC. The findings showed that MALAT1 levels were elevated at diagnosis, decreased during standard treatments, but notably increased at a distant metastatic site. This pattern suggests that MALAT1 may play a significant role in the cancer’s spread.
Disha Aggarwal, the graduate student who led the research, emphasized the importance of understanding MALAT1 fluctuations: “Even though MALAT1 has been implicated in different cancers, including breast cancer, nobody has looked at how MALAT1 levels change over treatment and disease progression.” This longitudinal approach provided a rare opportunity to study tissue samples collected throughout the patient’s treatment process over two and a half years, which included surgery, chemotherapy, radiation, and immunotherapy.
Despite a period of regression, the cancer eventually became metastatic, leading to the patient’s unfortunate passing three and a half years post-diagnosis. Nevertheless, her contributions to research may hold promise for future cancer therapies. CSHL Professor David Spector noted that researchers typically only observe an initial and final sample, but this study’s depth offers a comprehensive view of disease progression.
The insights gained from this research may influence future treatment strategies. Since 2015, Spector’s lab has collaborated with Ionis Pharmaceuticals to develop a drug targeting MALAT1. They are now in discussions with biotech companies to potentially initiate a clinical trial within the next few years.
Additionally, researchers are exploring whether MALAT1 levels can help predict the risk of cancer recurrence or metastasis. If successful, this could aid not only those diagnosed with TNBC but also patients with more common and less severe forms of breast cancer.
The study’s findings represent a pivotal moment in cancer research, as they could lead to targeted therapies aimed at improving patient outcomes. The ongoing investigation into MALAT1’s role in cancer progression highlights the potential for innovative approaches in the treatment of breast cancer.
For more information, see the study by Disha Aggarwal et al, titled “Longitudinal tracking of MALAT1 level over a breast cancer patient’s course of treatment and disease progression,” published in Molecular Therapy Oncology in 2025. DOI: 10.1016/j.omton.2025.201070.
