Loading
Life sciences · Journal article
Journal of Clinical Investigation · October 13, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Triple negaJve breast cancer (TNBC) is characterised by poor prognosis and limited treatment opJons, parJally due to therapy-resistant stem/progenitor cells driving metastasis. Elevated expression of the transcripJon factor MYBL2 is associated with aggressive disease, yet its role in BC stem/progenitor cells remains elusive. Here, we employed inducible MYBL2 downregulaJon in TNBC cell lines and paJent-derived models to invesJgate its funcJon and idenJfy potenJal vulnerabiliJes associated with its high expression. Our funcJonal and mechanisJc analyses reveal that high MYBL2 levels are criJcal for stem cell self-renewal, DNA repair, and replicaJon stress response and lowering MYBL2 impairs stemness and self-renewal both in vitro and in vivo. Accordingly, high-MYBL2 stem/progenitor cells exhibit increased sensiJvity to Polθ inhibitors which is lost upon MYBL2 downregulaJon due to transcripJonal suppression. Combining Polθ inhibitors with ATR inhibitors further enhances this sensiJvity, in vitro, ex vivo and in vivo. These findings suggest that dual Polθ/ATR inhibiJon represents a promising therapeuJc strategy to target TNBC stem/progenitor cells with high MYBL2 expression, highlighJng MYBL2 as a potenJal biomarker to straJfy paJents for Polθ inhibitor-based therapies in TNBC.