| First Author | Salvador-Barbero B | Year | 2020 |
| Journal | Cancer Cell | Volume | 37 |
| Issue | 3 | Pages | 340-353.e6 |
| PubMed ID | 32109375 | Mgi Jnum | J:285842 |
| Mgi Id | MGI:6400649 | Doi | 10.1016/j.ccell.2020.01.007 |
| Citation | Salvador-Barbero B, et al. (2020) CDK4/6 Inhibitors Impair Recovery from Cytotoxic Chemotherapy in Pancreatic Adenocarcinoma. Cancer Cell 37(3):340-353.e6 |
| abstractText | Inhibition of the cell-cycle kinases CDK4 and CDK6 is now part of the standard treatment in advanced breast cancer. CDK4/6 inhibitors, however, are not expected to cooperate with DNA-damaging or antimitotic chemotherapies as the former prevent cell-cycle entry, thus interfering with S-phase- or mitosis-targeting agents. Here, we report that sequential administration of CDK4/6 inhibitors after taxanes cooperates to prevent cellular proliferation in pancreatic ductal adenocarcinoma (PDAC) cells, patient-derived xenografts, and genetically engineered mice with Kras G12V and Cdkn2a-null mutations frequently observed in PDAC. This effect correlates with the repressive activity of CDK4/6 inhibitors on homologous recombination proteins required for the recovery from chromosomal damage. CDK4/6 inhibitors also prevent recovery from multiple DNA-damaging agents, suggesting broad applicability for their sequential administration after available chemotherapeutic agents. |
