2. Academic Validation
  3. CSNK1A1, KDM2A, and LTB4R2 Are New Druggable Vulnerabilities in Lung Cancer

CSNK1A1, KDM2A, and LTB4R2 Are New Druggable Vulnerabilities in Lung Cancer

  • Cancers (Basel). 2021 Jul 12;13(14):3477. doi: 10.3390/cancers13143477.
Elisabetta Sauta 1 2,  Francesca Reggiani 1,  Federica Torricelli 1,  Eleonora Zanetti 3,  Elena Tagliavini 3,  Giacomo Santandrea 3 4,  Giulia Gobbi 1,  Silvia Strocchi 1,  Massimiliano Paci 5,  Giovanna Damia 6,  Riccardo Bellazzi 2,  Davide Ambrosetti 7,  Alessia Ciarrocchi 1,  Valentina Sancisi 1
Affiliations

Affiliations

  • 1 Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
  • 2 Department of Electrical, Computer and Biomedical Engineering, University of Pavia, 27100 Pavia, Italy.
  • 3 Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
  • 4 Clinical and Experimental Medicine Ph.D. Program, University of Modena and Reggio Emilia, 41100 Modena, Italy.
  • 5 Thoracic Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
  • 6 Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.
  • 7 Department of Pharmacy and Biotechnology (FaBit), University of Bologna, 40126 Bologna, Italy.
PMID: 34298691 DOI: 10.3390/cancers13143477
Abstract

Lung Cancer is the leading cause of cancer-related human death. It is a heterogeneous disease, classified in two main histotypes, small-cell lung Cancer (SCLC) and non-small-cell lung Cancer (NSCLC), which is further subdivided into squamous-cell carcinoma (SCC) and adenocarcinoma (AD) subtypes. Despite the introduction of innovative therapeutics, mainly designed to specifically treat AD patients, the prognosis of lung Cancer remains poor. In particular, available treatments for SCLC and SCC patients are currently limited to platinum-based chemotherapy and Immune Checkpoint inhibitors. In this work, we used an integrative approach to identify novel vulnerabilities in lung Cancer. First, we compared the data from a CRISPR/Cas9 dependency screening performed in our laboratory with Cancer Dependency Map Project data, essentiality comprising information on 73 lung Cancer cell lines. Next, to identify relevant therapeutic targets, we integrated dependency data with pharmacological data and TCGA gene expression information. Through this analysis, we identified CSNK1A1, KDM2A, and LTB4R2 as relevant druggable essentiality genes in lung Cancer. We validated the antiproliferative effect of genetic or pharmacological inhibition of these genes in two lung Cancer cell lines. Overall, our results identified new vulnerabilities associated with different lung Cancer histotypes, laying the basis for the development of new therapeutic strategies.

Keywords

CRISPR/Cas9 screening; CSNK1A1; KDM2A; LTB4R2; lung cancer.

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