
Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer.
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 ζ-proteins, suggesting that Pol ζ-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.
Duke Scholars
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- Tumor Cells, Cultured
- Mutagenesis
- Mice
- Mad2 Proteins
- Lung Neoplasms
- Humans
- Drug Resistance, Neoplasm
- DNA-Directed DNA Polymerase
- DNA-Binding Proteins
- DNA Repair
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Cells, Cultured
- Mutagenesis
- Mice
- Mad2 Proteins
- Lung Neoplasms
- Humans
- Drug Resistance, Neoplasm
- DNA-Directed DNA Polymerase
- DNA-Binding Proteins
- DNA Repair