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Tracing back primed resistance in cancer via sister cells

ABSTRACT: Exploring non-genetic evolution of cell states during cancer treatments has become attainable by recent advances in lineage-tracing methods. However, transcriptional changes that drive cells into resistant fates may be subtle, necessitating high resolution analysis. We developed ReSisTrace that uses shared transcriptomic features of synchronized sister cells to predict the states that prime treatment resistance. We applied ReSisTrace in ovarian cancer cells to dissect primed resistance against olaparib, carboplatin or natural killer (NK) cells, and discovered a novel connection between DNA repair deficiency and susceptibility to NK cells. Furthermore, we identified small molecules driving cells to sensitive states prior to treatment. In summary, ReSisTrace resolves pre-existing transcriptional features of treatment vulnerability, facilitating both molecular patient stratification for personalized treatments and discovery of synergistic pre-sensitizing therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223003 | GEO | 2023/12/22

REPOSITORIES: GEO

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