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

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. Des...

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Bibliographic Details
Published in:Cancers 2021-07, Vol.13 (14), p.3477
Main Authors: Sauta, Elisabetta, Reggiani, Francesca, Torricelli, Federica, Zanetti, Eleonora, Tagliavini, Elena, Santandrea, Giacomo, Gobbi, Giulia, Strocchi, Silvia, Paci, Massimiliano, Damia, Giovanna, Bellazzi, Riccardo, Ambrosetti, Davide, Ciarrocchi, Alessia, Sancisi, Valentina
Format: Article
Language:English
Subjects:
Adenocarcinoma
Cancer therapies
Chemotherapy
Clinical trials
CRISPR
Gene expression
Genomes
Genomics
Immune checkpoint inhibitors
Lung cancer
Medical innovations
Medical prognosis
Mutation
Non-small cell lung carcinoma
Patients
Small cell lung carcinoma
Software
Therapeutic applications
Therapeutic targets
Tumor cell lines
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13143477