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Tessari et al. J Cancer Metastasis Treat 2020;6:18 Journal of Cancer
DOI: 10.20517/2394-4722.2020.32 Metastasis and Treatment

Perspective Open Access

RANBP9 as potential therapeutic target in non-small
cell lung cancer

Anna Tessari , Shimaa H. A. Soliman 1,2,3 , Arturo Orlacchio , Marina Capece , Joseph M. Amann , Rosa
1
3
1
1
Visone , David P. Carbone , Dario Palmieri , Vincenzo Coppola 1
1
2
4
1 Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University and Arthur G. James Comprehensive
Cancer Center, Columbus, OH 43210, USA.
2 Department of Medicine, Dentistry and Biotechnology, G. d’Annunzio University of Chieti, Chieti 66100, Italy.
3 Current address: Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine,
Chicago, IL 60611, USA.
4 Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University and Arthur G.
James Comprehensive Cancer Center, Columbus, OH 43210, USA.
Correspondence to: Dr. Vincenzo Coppola, Department of Cancer Biology and Genetics, College of Medicine, The Ohio State
University and Arthur G. James Comprehensive Cancer Center, 460 West 12th Avenue, Columbus, OH 43210, USA.
E-mail: vincenzo.coppola@osumc.edu
How to cite this article: Tessari A, Soliman SHA, Orlacchio A, Capece M, Amann JM, Visone R, Carbone DP, Palmieri D, Coppola
V. RANBP9 as potential therapeutic target in non-small cell lung cancer. J Cancer Metastasis Treat 2020;6:18.
http://dx.doi.org/10.20517/2394-4722.2020.32
Received: 7 Apr 2020 First Decision: 6 May 2020 Revised: 17 May 2020 Accepted: 4 Jun 2020 Published: 24 Jun 2020

Science Editor: Ciro Isidoro Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths in the Western world.
Despite progress made with targeted therapies and immune checkpoint inhibitors, the vast majority of patients
have to undergo chemotherapy with platinum-based drugs. To increase efficacy and reduce potential side effects,
a more comprehensive understanding of the mechanisms of the DNA damage response (DDR) is required. We
have shown that overexpressby live cell imaging (Incuyion of the scaffold protein RAN binding protein 9 (RANBP9)
is pervasive in NSCLC. More importantly, patients with higher levels of RANBP9 exhibit a worse outcome from
treatment with platinum-based drugs. Mechanistically, RANBP9 exists as a target and an enabler of the ataxia
telangiectasia mutated (ATM) kinase signaling. Indeed, the depletion of RANBP9 in NSCLC cells abates ATM
activation and its downstream targets such as pby live cell imaging (Incuy53 signaling. RANBP9 knockout cells
are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related (ATR) kinase but not to
ATM inhibition. The absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-
Polymerase (PARP) resulting in a “BRCAness-like” phenotype. In summary, as a result of increased sensitivity
to DNA damaging drugs conferred by its ablation in vitro and in vivo, RANBP9 may be considered as a potential
target for the treatment of NSCLC. This article aims to report the results from past and ongoing investigations

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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