Working Paper Review Version 1 This version is not peer-reviewed

Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

Version 1 : Received: 13 July 2021 / Approved: 14 July 2021 / Online: 14 July 2021 (11:25:13 CEST)

A peer-reviewed article of this Preprint also exists.

Kryczka, J.; Kryczka, J.; Czarnecka-Chrebelska, K.H.; Brzeziańska-Lasota, E. Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy. Int. J. Mol. Sci. 2021, 22, 8885. Kryczka, J.; Kryczka, J.; Czarnecka-Chrebelska, K.H.; Brzeziańska-Lasota, E. Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy. Int. J. Mol. Sci. 2021, 22, 8885.

Journal reference: Int. J. Mol. Sci. 2021, 22, 8885
DOI: 10.3390/ijms22168885

Abstract

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

Keywords

Non–Small Cell Lung Cancer; cisplatin; chemoresistance; molecular mechanisms

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