Cell Migration Related to MDR—Another Impediment to Effective Chemotherapy?

Kryczka, Jakub; Boncela, Joanna

doi:10.3390/molecules23020331

Cited by 11 publications

(22 citation statements)

References 142 publications

(178 reference statements)

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“…However, this treatment entails a multipronged adaptive response in malignant cells, which renders them less susceptible to the antiproliferative and cytotoxic effects of the drugs, resulting in the resumption of proliferation [16,20,21]. These mechanisms allow the cancer cell to survive and progress in human organisms, thus develop resistance to therapy [24]. Such resistance is a significant cause for therapeutic failure of NSCLC, leading to tumour recurrence and disease progression [25].…”

Section: Mechanisms Underlying Cisplatin Resistancementioning

confidence: 99%

“…A significant role is played by tolerance or repair of cisplatin-DNA adducts. In addition, resistance has been associated with the induction of anti-apoptotic signals, the active efflux of drugs from the cell cytoplasm, epigenetic regulation by miRNA, deregulation of growth regulatory pathways by acquiring growth factor independence, suppression of the immune system, and low expression of antigens that activate T lymphocyte cells (mimicry) [16,24,26,27]. All these mechanisms appear to play crucial roles in cisplatin resistance.…”

Section: Mechanisms Underlying Cisplatin Resistancementioning

confidence: 99%

“…Sci. 2021, 22, x FOR PEER REVIEW 3 of 20 cell cytoplasm, epigenetic regulation by miRNA, deregulation of growth regulatory pathways by acquiring growth factor independence, suppression of the immune system, and low expression of antigens that activate T lymphocyte cells (mimicry) [16,24,26,27]. All these mechanisms appear to play crucial roles in cisplatin resistance.…”

Section: Mechanisms Underlying Cisplatin Resistancementioning

confidence: 99%

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Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

Kryczka

Czarnecka-Chrebelska

et al. 2021

IJMS

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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.

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Section: Mechanisms Underlying Cisplatin Resistancementioning

confidence: 99%

Section: Mechanisms Underlying Cisplatin Resistancementioning

confidence: 99%

Section: Mechanisms Underlying Cisplatin Resistancementioning

confidence: 99%

See 1 more Smart Citation

Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy

Kryczka

Czarnecka-Chrebelska

et al. 2021

IJMS

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“…Hematologic cancers, consisting of leukemia, lymphoma, and myeloma, originate and progress in primary or secondary lymphoid organs and develop and spread differently from solid tumors (25). The main characteristic of these types of cancer is their ability to affect bone marrow hematopoietic precursors that, from the beginning, are no longer restricted to a single region of the body, manifesting 1,2,3,4,5,6 Superscript numbers refer to the combination of each parental cell line, correspondent drug and derived resistant cell line.…”

Section: Application Of Cell Lines In Experimental Oncologymentioning

confidence: 99%

“…drugs that directly or indirectly damage DNA, DNA damage response mechanisms can reverse drug induced damages (6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Establishment of Drug-resistant Cell Lines as a Model in Experimental Oncology: A Review

et al. 2019

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Many types of cancer are initially susceptible to chemotherapy, but during treatment, patients may develop resistance to therapy. Knowing that acquisition of drug resistance is a major clinical problem in antineoplastic treatment, the present work aimed to present, through a literature review, the development of chemoresistant cells lines as a model in experimental oncology. A total of 110 drugresistant cell lines, mainly from lung tumors and leukemias, have been developed. In addition, it has been observed that the drugs used for induction of resistance represented the drugs used for first-line treatment of each neoplasia, since the ideal chemotherapeutic treatment to induce resistance in vitro aims at a better modulation of the therapeutic response in order to better study the mechanisms of resistance. Normal tissue controls the production and release of growth promoting signals that regulate the initiation and progression of the cell cycle, ensuring cellular homeostasis and maintainance of healthy tissue architecture and function. Cancer cells exhibit deregulation of these signals and may acquire the ability to maintain continuous and abnormal proliferative signaling, inhibition of growth suppressors, resistance to cell death, replicative immortality, angiogenesis and metastasis that leads to an inadequate and pathogenic functioning of the tissue in which they occur (1-4). The literature shows that, in the tumor model, cancer cells originate from a single cell that has important stem cell characteristics, including the unlimited potential for replication and mechanisms of protection from xenobiotic agents. These findings have a significant effect on cancer treatment, since traditional antineoplastic treatment was based on the assumption that all somatic cells have a similar malignant potential, and the lack of specificity in combating these characteristics has rendered the therapies ineffective in providing a lasting response to cancer (5, 6). Chemotherapy is one of the pillars of clinical cancer treatment, but its outcome usually culminates in multidrug resistance (MDR), a phenomenon that can be found in several cells present in the tumor microenvironment, drastically restricting and the curative effect of drugs for a variety of tumors (7-9). Although many types of cancer are initially susceptible to chemotherapy, over the course of the therapeutic regimen, some patients may develop therapeutic resistance, due to several intracellular mechanisms including genetic and epigenetic changes in signaling pathways of survival, drug metabolizing enzymes and drug efflux pump mechanisms. Epigenetic modifications also act as an important set of mechanisms that lead to resistance in cancer treatment, and the main ones include DNA methylation and histone acetylation that can influence carcinogenesis because they deregulate normal expression of genes (Figure 1) (10, 11). The most studied mechanism of resistance to drugs against cancer involves the reduction of the intracellular concentration of the drug by increasing drug ...

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