Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

Abstract

Cancer cells utilise several 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). Because 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 summarises the main mechanisms involved in cisplatin resistance and interactions between cisplatin-resistant cancer cells and the tumour 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 encode 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.

Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures

“…The amount of cisPt detected in the nuclei of resistant cells after 16 h of incubation is similar to the amount observed in wt nuclei after 8 h of incubation with cisPt. The relatively high concentration of cisPt in the resistant cell nuclei underpins that cisPt resistance in NSCLC is due to a multifaceted mechanism [42].…”

The Role of Circular RNAs in the Drug Resistance of Cancers

“…However, the genes in cancer cells commonly demonstrate mutations, including apoptotic genes, which often cause dysfunction. This may result in the occurrence of resistance to chemotherapeutics, as any interference that mediates the activation of anti-apoptotic pathways or suppression of pro-apoptotic signal transduction is a potential mechanism of drug resistance ( 25 ).…”

A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non–Small Cell Lung Cancer

“…Cisplatin-based combination chemotherapy is the standard first-line therapy for patients with unresectable advanced NSCLC ( Bluthgen and Besse, 2015 ), and platinum compounds are considered to be the most effective anticancer drugs in the clinical treatment of NSCLC at present. However, resistance to cisplatin can be induced by multiple factors ( Rose et al, 2014 ; Kryczka et al, 2021 ), and resistance to cisplatin in lung cancer is a key factor affecting the therapeutic effect. Zhu et al (2018) found that triptolide at non-cytotoxic concentrations increased the sensitivity of A549 cells to cytotoxic chemotherapeutic agents (cisplatin, etoposide, and erythromycin) and triptolide increased the chemotherapy sensitivity of xenotransplanted tumors in vitro .…”