Researchers at Cold Spring Harbor Laboratory (CSHL) have made significant strides in understanding the progression of triple-negative breast cancer (TNBC) by studying the long non-coding RNA known as MALAT1. Traditionally, cancer therapies focus on targeting protein-coding genes that contribute to tumor development. In a groundbreaking study published in Molecular Therapy: Oncology, CSHL scientists tracked MALAT1 levels throughout the treatment journey of a single patient, revealing crucial insights into the disease’s behavior.
The study examined the case of a 59-year-old woman diagnosed with stage 1 TNBC. Initially, MALAT1 levels were elevated at the time of diagnosis. As the patient underwent standard treatments—including surgery, chemotherapy, radiation, and immunotherapy—researchers observed a decrease in MALAT1 levels. Notably, these levels surged when the cancer metastasized to a distant site, suggesting a potential role for MALAT1 in the spread of TNBC.
According to Disha Aggarwal, the graduate student who led the study, “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 research offers a unique perspective on a treatment target that has not been thoroughly investigated in the context of ongoing treatment.
The patient experienced a period of regression, but ultimately succumbed to the disease three and a half years after her diagnosis. The depth of tissue samples collected during her treatment journey provided researchers with an unprecedented opportunity to analyze the evolving role of MALAT1. David Spector, a professor at CSHL, noted, “Researchers typically get to see an initial sample and an end sample, but not progressive samples in the depth that we were able to look at here.”
The findings from this study hold promise for future cancer treatments. Since 2015, Spector’s lab has collaborated with Ionis Pharmaceuticals to develop a drug targeting MALAT1. They are currently in discussions with biotech companies to initiate clinical trials within the next few years.
The potential applications of this research extend beyond TNBC. Spector’s lab is also investigating whether MALAT1 levels could help predict the risk of cancer recurrence or metastasis. If successful, this could guide treatment strategies not only for women diagnosed with TNBC but also for patients with more common and less aggressive forms of breast cancer.
With the ongoing investigation into MALAT1’s role in TNBC, the hope is that these findings will pave the way for new therapeutic approaches, ultimately improving patient outcomes in the fight against breast cancer.
For further reading, see the study: Disha Aggarwal et al, “Longitudinal tracking of MALAT1 level over a breast cancer patient’s course of treatment and disease progression,” Molecular Therapy: Oncology (2025). DOI: 10.1016/j.omton.2025.201070.
