Molecular barcodes offer insight into cancer
New advances in molecular barcoding offer exciting possibilities, especially in cancer research. Over the years, molecular barcoding involved generating specific nucleic acids or proteins within cells to trace lineages across generations to observe results. However, this approach has required researchers to “kill” cells to harvest signature genetic information. Recent advances make it possible to observe how isolated cells—especially tumor cells—can be observed live and in real-time.
How can this novel approach be used? Anna Obenauf at the Memorial Sloan Kettering Cancer Center was able to generate a barcoded oncolytic cell line in mice, introduce a treatment, and analyze the impact. Obenauf and her team were able to evaluate the effect treatment had and more clearly understand the mechanics behind mutations that resulted in drug resistance. Using CRISPR–Cas9 gene editing to target barcoded cells, Obenauf and her team were then able to draw an important conclusion: tumor cells became resistant to treatment in response to the introduced drug, providing direction for future follow-up treatment.
Similarly, Barbara Grüner and her team at University Hospital Essen in Germany used barcoding to study the efficacy of treatments after metastasization. Starting with pancreatic cancer, they studied how a treatment reduced the number of barcoded cells that spread to lungs in mice. Thanks to the barcoding approach, they were able to achieve significant results working with a fraction of the number of mice that would have been required using other techniques.
Another approach has been to use barcodes to “illuminate” the spatial organization of cancer. Garry Nolan and Julien Sage at Stanford University used protein-based barcodes that relied on a combination of antibodies associated with a heavy-metal atom. The team used multiplexed ion beam imaging (MIBI) to visualize three-peptide barcodes, and they were then able to explore the structure of tumors.
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Source: Madhusoodanan. Nature; https://doi.org/10.1038/d41586-022-00798-w (2022)