Australian scientists have made a groundbreaking discovery in cancer research, revealing that DNA barcoding can be utilized to track cancer cells in both solid and liquid biopsies. This innovative approach has the potential to revolutionize breast cancer diagnosis and treatment, offering a more comprehensive understanding of tumor diversity. Tumors, composed of various cancer cells with differing aggressiveness and treatment sensitivity, require further exploration to fully comprehend the role of solid and liquid biopsies in capturing this diversity. DNA barcoding technology, employing lentiviruses to label individual cancer cells with DNA tags, serves as a powerful tool to study cancer heterogeneity. These tags, acting as unique identifiers, can be tracked and identified in tumor cells and matched biopsies, providing valuable insights into tumor composition and heterogeneity. Researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI), WEHI, and Peter MacCallum Cancer Centre have optimized DNA barcoding techniques, leading to a significant finding: tumors in different models shed varying amounts of DNA into the bloodstream, even when their cancer cell makeup appears similar. This discovery, achieved for the first time, enables the detection of DNA barcodes shed by primary tumors in blood and plasma samples. The study's findings indicate that DNA tag detectability varies across models, with some showing low recovery even in highly metastatic cases. This suggests that DNA shedding is model-specific, potentially leading to false-negative liquid biopsy results. Dr. Antonin Serrano, a postdoctoral researcher at the University of Melbourne, highlights the key findings, emphasizing the ability of DNA barcoding to investigate entire tumors, solid biopsies, and liquid biopsies, and accurately quantify tumor heterogeneity. The research also reveals that DNA shedding in the bloodstream varies widely, influenced by factors such as necrosis and tumor burden, and across different preclinical models. Furthermore, the study uncovers a higher barcode diversity in the center of primary tumors compared to the periphery, which has implications for interpreting solid biopsies. Prof. Delphine Merino, Laboratory Head at ONJCRI and senior author of the Molecular Systems Biology paper, suggests that both liquid and solid biopsies are generally representative of tumor composition, but results vary between tumors. This implies that combining both strategies may provide a more accurate representation of the disease. Co-senior author and breast cancer clinician Prof. Sarah-Jane Dawson emphasizes the non-invasive nature of liquid biopsies for monitoring disease progression, and the research's potential to enhance their use in clinical settings. The study's findings have significant implications for breast cancer research, with 20,336 new cases diagnosed in Australia in 2025, resulting in an estimated 3,353 deaths. The research team, including Dr. Tom Weber and Prof. Shalin Naik, has published their findings in the Molecular Systems Biology journal, offering a promising avenue for future cancer research and treatment.
