New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin

Ciocan-Cârtiţă, Cristina Alexandra; Jurj, Ancuța; Ráduly, Lajos; Cojocneanu, Roxana; Moldovan, Alin; Pileczki, Valentina; Pop, Laura; Budişan, Liviuţa; Braicu, Cornelia; Korban, Schuyler S.; Berindan‐Neagoe, Ioana

doi:10.1007/s11010-020-03881-w

Cited by 18 publications

(11 citation statements)

References 61 publications

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“…The mechanisms of primary or acquired chemoresistance to doxorubicin still remain to be deciphered. Thus, our study is focused on the regulatory pathways responsible for resistance to therapy and possible specific targets that could help optimize patient responses to this drug [10,11]. Chemoresistance is correlated with genetic alterations, that can activate pro-survival signaling, DNA damage repair, drug efflux or epithelial-mesenchymal transition [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells

Ciocan-Cârtiţă

Jurj

Zănoagă

et al. 2020

J Exp Clin Cancer Res

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Background Triple negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and an unfavorable prognosis rate. Due to the lack of surface receptors, TNBC must be intensely investigated in order to establish a suitable treatment for patients with this pathology. Chemoresistance is an important reason for therapeutic failure in TNBC. Method The aim of this study was to investigate the effect of doxorubicin in TNBC cell lines and to highlight cellular and molecular alterations after a long exposure to doxorubicin. Results The results revealed that doxorubicin significantly increased the half maximal inhibitory concentration (IC50) values at P12 and P24 compared to parenteral cells P0. Modifications in gene expression were investigated through microarray technique, and for detection of mutational pattern was used Next Generation Sequencing (NGS). 196 upregulated and 115 downregulated genes were observed as effect of multiple dose exposure, and 15 overexpressed genes were found to be involved in drug resistance. Also, the presence of some additional mutations in both cell lines was observed. Conclusion The outcomes of this research may provide novel biomarkers for drug resistance in TNBC. Also, this activity can highlight the potential mechanisms associated with drug resistance, as well as the potential therapies to counteract these mechanisms.

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Section: Introductionmentioning

confidence: 99%

New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells

Ciocan-Cârtiţă

Jurj

Zănoagă

et al. 2020

J Exp Clin Cancer Res

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“…In this regard, the tumor stiffness is increased and enhances tumor growth [95]. It is already known that TGFβ has a dual role in cancer [96]. In the early stages of cancer, the role of TGFβ is to inhibit tumor cell proliferation, while, in the later stages of cancer, it is to stimulate the malignant progression and metastasis of cancer cells [97].…”

Section: Detailed Role In Cancer Referencementioning

confidence: 99%

The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes?

Jurj

Ionescu

Berindan‐Neagoe

et al. 2022

J Exp Clin Cancer Res

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The extracellular matrix (ECM) is an important component of the tumor microenvironment (TME), having several important roles related to the hallmarks of cancer. In cancer, multiple components of the ECM have been shown to be altered. Although most of these alterations are represented by the increased or decreased quantity of the ECM components, changes regarding the functional alteration of a particular ECM component or of the ECM as a whole have been described. These alterations can be induced by the cancer cells directly or by the TME cells, with cancer-associated fibroblasts being of particular interest in this regard. Because the ECM has this wide array of functions in the tumor, preclinical and clinical studies have assessed the possibility of targeting the ECM, with some of them showing encouraging results. In the present review, we will highlight the most relevant ECM components presenting a comprehensive description of their physical, cellular and molecular properties which can alter the therapy response of the tumor cells. Lastly, some evidences regarding important biological processes were discussed, offering a more detailed understanding of how to modulate altered signalling pathways and to counteract drug resistance mechanisms in tumor cells.

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“…As for drug discovery, NGS has been successfully used in various areas of drug discovery, beginning with target identification, compound screening, biomarker discovery, identification of biopharmaceuticals, drug resistance, and vaccine discovery [166][167][168]. Those steps involved in drug discovery where NGS could be of particular use are presented in Figure 4.…”

Section: Next Generation Sequencing For Drug Discoverymentioning

confidence: 99%

Microarrays and NGS for Drug Discovery

Pop¹,

Zănoagă²,

Chiroi³

et al. 2021

Drug Design - Novel Advances in the Omics Field and Applications

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Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options.

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New perspectives in triple-negative breast cancer therapy based on treatments with TGFβ1 siRNA and doxorubicin

Cited by 18 publications

References 61 publications

New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells

New insights in gene expression alteration as effect of doxorubicin drug resistance in triple negative breast cancer cells

The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes?

Microarrays and NGS for Drug Discovery

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