| First Author | Cánovas B | Year | 2018 |
| Journal | Cancer Cell | Volume | 33 |
| Issue | 6 | Pages | 1094-1110.e8 |
| PubMed ID | 29805078 | Mgi Jnum | J:262539 |
| Mgi Id | MGI:6162341 | Doi | 10.1016/j.ccell.2018.04.010 |
| Citation | Canovas B, et al. (2018) Targeting p38alpha Increases DNA Damage, Chromosome Instability, and the Anti-tumoral Response to Taxanes in Breast Cancer Cells. Cancer Cell 33(6):1094-1110.e8 |
| abstractText | Breast cancer is the second leading cause of cancer-related death among women. Here we report a role for the protein kinase p38alpha in coordinating the DNA damage response and limiting chromosome instability during breast tumor progression, and identify the DNA repair regulator CtIP as a p38alpha substrate. Accordingly, decreased p38alpha signaling results in impaired ATR activation and homologous recombination repair, with concomitant increases in replication stress, DNA damage, and chromosome instability, leading to cancer cell death and tumor regression. Moreover, we show that pharmacological inhibition of p38alpha potentiates the effects of taxanes by boosting chromosome instability in murine models and patient-derived xenografts, suggesting the potential interest of combining p38alpha inhibitors with chemotherapeutic drugs that induce chromosome instability. |
