Researchers have identified a potentially overlooked factor in the progression of advanced breast cancer: a rare type of circulating tumor cell known as dual-positive (DP) cells. These cells, which exhibit characteristics of both tumor cells and immune cells, appear to be linked to shorter survival times, particularly in patients with aggressive forms of the disease. The findings, published March 11 in Science Translational Medicine, underscore the need for further investigation into these unusual cells and their potential role in treatment resistance.
Circulating tumor cells (CTCs) are cancer cells that have detached from the primary tumor and are traveling through the bloodstream, potentially seeding new tumors in other parts of the body. DP cells are a subset of CTCs that uniquely express markers found on both cancer cells and immune cells, suggesting they may arise from a fusion between the two. Recent studies have hinted at the significance of DP cells in other cancers, including melanoma and pancreatic cancer, but their role in breast cancer has remained largely unexplored. Understanding these cells could lead to improved strategies for predicting prognosis and developing more effective therapies for advanced breast cancer.
The Link Between DP Cells and Survival Rates
The study, led by investigators at Weill Cornell Medicine and NewYork-Presbyterian, analyzed blood samples from 340 women with advanced breast cancer. Researchers identified at least one DP cell in nearly half of the patients (44.7%). However, the presence of three or more DP cells was strongly associated with significantly reduced survival. Patients with three or more DP cells had a median survival of just 23.5 months, compared to 33.6 months for those with fewer than three. This association was further validated in an additional group of 51 patients treated at NewYork-Presbyterian/Weill Cornell Medical Center.
“A better understanding of the role of these unusual cells in triple-negative breast cancer might assist us devise better treatments and methods for predicting and monitoring treatment responses,” said Dr. Carolina Reduzzi, assistant professor of cancer biology research in medicine at Weill Cornell Medicine and co-first author of the study. Dr. Eleonora Nicolò, instructor of cancer research in medicine at Weill Cornell Medicine, also served as a co-first author. Both researchers are part of the laboratory led by Dr. Massimo Cristofanilli, professor of medicine in the Division of Hematology and Medical Oncology at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.
How DP Cells Differ from Traditional Cancer Cells
The research suggests that DP cells may have a unique biology that sets them apart from more conventional circulating tumor cells. While ordinary CTCs are known to contribute to metastasis, DP cells appear to be capable of seeding new tumors even with fewer genetic abnormalities. Approximately 29% of DP cells analyzed exhibited copy number alterations, a common feature of tumors, but a lower percentage than observed in ordinary CTCs. The team found that 60% of analyzed DP cells bore a marker characteristic of macrophages, a type of immune cell, supporting the hypothesis that these cells originate from a fusion between tumor cells and immune cells.
Animal models also provided crucial insights. Researchers were only able to detect DP cells in breast cancer mouse models when the mice had intact immune systems, suggesting that the immune system plays a critical role in their formation or survival. Dr. Cristofanilli, who is also the scientific director and head of the Liquid Biopsy Platform at the Englander Institute for Precision Medicine and the associate director of precision oncology at the Sandra and Edward Meyer Cancer Center, emphasized the need to target these cells specifically. “Our current therapies target ordinary cancer cells, but DP cells have a different biology,” he stated. “We need to understand that better if we’re going to target them effectively.”
Future Research and Implications for Treatment
The research team is now focused on comprehensively characterizing the gene expression patterns of DP cells to better understand their origins and function. This deeper understanding could pave the way for the development of targeted therapies specifically designed to eliminate these cells and improve outcomes for patients with advanced breast cancer. The findings highlight the importance of liquid biopsies – analyzing circulating tumor cells and other biomarkers in the blood – as a tool for monitoring cancer progression and treatment response.
This research underscores the complex interplay between cancer cells and the immune system, and the potential for harnessing this knowledge to develop more effective cancer treatments. Further investigation into DP cells and their unique characteristics promises to refine our understanding of breast cancer metastasis and ultimately improve patient care.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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