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Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer.

Publication ,  Journal Article
Vassel, F-M; Bian, K; Walker, GC; Hemann, MT
Published in: Proc Natl Acad Sci U S A
November 17, 2020

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.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 17, 2020

Volume

117

Issue

46

Start / End Page

28922 / 28924

Location

United States

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
 

Citation

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Vassel, F.-M., Bian, K., Walker, G. C., & Hemann, M. T. (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. https://doi.org/10.1073/pnas.2016067117
Vassel, Faye-Marie, Ke Bian, Graham C. Walker, and Michael T. Hemann. “Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer.Proc Natl Acad Sci U S A 117, no. 46 (November 17, 2020): 28922–24. https://doi.org/10.1073/pnas.2016067117.
Vassel F-M, Bian K, Walker GC, Hemann MT. Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28922–4.
Vassel, Faye-Marie, et al. “Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer.Proc Natl Acad Sci U S A, vol. 117, no. 46, Nov. 2020, pp. 28922–24. Pubmed, doi:10.1073/pnas.2016067117.
Vassel F-M, Bian K, Walker GC, Hemann MT. Rev7 loss alters cisplatin response and increases drug efficacy in chemotherapy-resistant lung cancer. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28922–28924.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

November 17, 2020

Volume

117

Issue

46

Start / End Page

28922 / 28924

Location

United States

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