| First Author | Vassel FM | Year | 2020 |
| Journal | Proc Natl Acad Sci U S A | Volume | 117 |
| Issue | 46 | Pages | 28922-28924 |
| PubMed ID | 33144509 | Mgi Jnum | J:298607 |
| Mgi Id | MGI:6477531 | Doi | 10.1073/pnas.2016067117 |
| Citation | Vassel FM, et al. (2020) Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer. Proc Natl Acad Sci U S A 117(46):28922-28924 |
| abstractText | Cisplatin is a standard of care for lung cancer, yet platinum therapy rarely results in substantial tumor regression or a dramatic extension in patient survival. Here, we examined whether targeting Rev7 (also referred to as Mad2B, Mad2L2, and FANCV), a component of the translesion synthesis (TLS) machinery, could potentiate the action of cisplatin in non-small cell lung cancer (NSCLC) treatment. Rev7 loss led to an enhanced tumor cell sensitivity to cisplatin and dramatically improved chemotherapeutic response in a highly drug-resistant mouse model of NSCLC. While cisplatin monotherapy resulted in tumor cell apoptosis, Rev7 deletion promoted a cisplatin-induced senescence phenotype. Moreover, Rev7 deficiency promoted greater cisplatin sensitivity than that previously shown following targeting of other Pol zeta-proteins, suggesting that Pol zeta-dependent and -independent roles of Rev7 are relevant to cisplatin response. Thus, targeting Rev7 may represent a unique strategy for altering and enhancing chemotherapeutic response. |
