ReSisTrace is an innovative technique that tracks cancer cell resistance by utilizing hereditary barcodes, exposing how some cells avert treatment. This insight guides the advancement of drugs that can turn resistant cells back to a state where they can be efficiently targeted by existing treatments. Credit: SciTechDaily.com
By genetically identifying cancer cells, ReSisTrace reveals pre-existing resistant states, resulting in targeted treatments that avoid treatment evasion, providing a brand-new frontier in customized cancer care.
In lots of cancers, such as ovarian cancer, each round of chemotherapy eliminates most of cancer cells, while a little population of them endures through treatment.
Labeling Cancer Cells With Genetic Barcodes
“In ReSisTrace, we label cancer cells uniquely with genetic barcodes and allow them to divide once, so that we get two identical sister cells that share the same barcode. We then analyze single-cell gene expression from half of the cells before the treatment, while treating the other half with chemotherapy, or other anti-cancer treatment. From the surviving cells, we can identify the barcodes of resistant cells. Using their sister cells analyzed before the treatment, we can discover how the cells that will survive through treatment differ from the pre-sensitive cells, thus revealing the pre-existing resistant states,” states Jun Dai, PhD trainee in Anna Vähärautio’s group, who established the approach to trace sis cells.
Discovery of Resistant Cell States
The technique was used to expose resistant cell states versus chemotherapy, targeted treatment, or natural resistance in top-quality serous ovarian cancer.
“We discovered that genes connected with proteostasis and mRNA monitoring are essential to discuss pre-existing treatment resistance. Interestingly, we discovered that < period class =(**************************************** )aria-describedby ="tt" data-cmtooltip ="<div class=glossaryItemTitle>DNA</div><div class=glossaryItemBody>DNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that coil around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that carries genetic instructions for development, functioning, growth, and reproduction. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).</div>" data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]" tabindex ="0" function ="link" > DNA repair work shortage which is extremely typical in ovarian cancer, sensitized these cells to not just chemotherapy and PARP inhibitors however likewise to NK killing,” statesShuyuZheng, a PhD trainee fromJingTang’s group, who led the computational analysis.
Predicting andOvercomingResistance
AssociateProfessorJingTang’s lab then leveraged the exposed gene expression modifications to anticipate little particles that might move the cells from a resistant state to a delicate state.
“We developed a computational method to correlate the resistant states with the gene expression changes induced by a drug. Ideally, if a drug can reverse the resistant cells’ gene expression profiles, then it can be considered as a potential hit to overcome the resistance,” statesAssociate Professor(***************************************************************************************************************** )Tang, a group leader inSystems (************************************************************************************************ )Research program at theUniversity ofHelsinki
(************************************************************************************** )discovered that the majority of the anticipated little particles undoubtedly altered the gene expression patterns of cancer cells towards delicate states.Most notably, after including these drugs, cancer cells were substantially more conscious carboplatin, PARP inhibitor or NK killing, showing that the pre-resistance states recognized by ReSisTrace were functionally appropriate and targetable.
“Our novel experimental-computational approach really leverages the power of single-cell omics and pharmacological data integration,” Associate Professor Jing Tang sums up.
Broad Applicability in Cancer Treatment
“The method we developed reveals the features of cells that will — in the future — become resistant to anti-cancer treatments by coupling cell state and fate in sister cell resolution. It is widely applicable to identify and target pre-existing resistant cell states across cancer types, as well as against different treatment modalities, including immunotherapies. Our approach paves the way for the development of sequential cancer therapies that can block resistance before it even emerges,” concludes Anna Vähärautio, K. Albin Johansson Cancer Research Fellow, Foundation for the Finnish Cancer Institute and a group leader in the Systems Oncology Research program at the University of Helsinki.
Reference: “Tracing back primed resistance in cancer via sister cells” by Jun Dai, Shuyu Zheng, Mat ías M. Falco, Jie Bao, Johanna Eriksson, Sanna Pikkusaari, Sofia Forst én, Jing Jiang, Wenyu Wang, Luping Gao, Fernando Perez-Villatoro, Olli Dufva, Khalid Saeed, Yinyin Wang, Ali Amiryousefi, Anniina Färkkilä, Satu Mustjoki, Liisa Kauppi, Jing Tang and Anna Vähärautio, 7 February 2024, < period class ="glossaryLink" aria-describedby ="tt" data-cmtooltip ="<div class=glossaryItemTitle>Nature Communications</div><div class=glossaryItemBody><em>Nature Communications</em> is a peer-reviewed, open-access, multidisciplinary, scientific journal published by Nature Portfolio. It covers the natural sciences, including physics, biology, chemistry, medicine, and earth sciences. It began publishing in 2010 and has editorial offices in London, Berlin, New York City, and Shanghai. </div>" data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]" tabindex ="0" function ="link" >NatureCommunications
DOI:10(****************************************************** )/ s41467-024-45478 -7(********** )
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