Genetic Influences in Breast Cancer Drug Resistance

Daniyal, Adhitiya; Santoso, Ivana; Gunawan, Nadira Hasna Putri; Barliana, Melisa Intan; Abdulah, Rizky

doi:10.2147/bctt.s284453

Cited by 12 publications

(9 citation statements)

References 187 publications

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“…The effectiveness of BC therapy using different modes of treatment with several anti-cancer drugs including classical chemotherapy, hormone, and targeted therapy tools has been extensively studied and discussed in the last decade [ 28 ]. However, despite the considerable progress that has been made in hormone-responsive breast cancer treatment, multi-drug resistance is a serious clinical problem, underlining the need for further advances [ 29 ]. Therefore, new therapeutic solutions are being sought that are effective in the treatment of breast tumors that are not susceptible to conventional treatment regimens.…”

Section: Discussionmentioning

confidence: 99%

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Wawruszak

Łuszczki

Hałasa

et al. 2021

IJMS

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Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.

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Section: Discussionmentioning

confidence: 99%

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Wawruszak

Łuszczki

Hałasa

et al. 2021

IJMS

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“…Among these BC subtypes, TNBC is associated with poor survival mediated by treatment resistance, and it is the most difficult to treat with curative intent (Liao et al, 2021). Several drugs (e.g., anthracyclines and trastuzumab) have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of BC; however, issues such as poor efficacy, toxicity, adverse drug reactions, and the emergence of drug resistance have limited their clinical use (Brower, 2013;Cameron et al, 2017;Shah and Gradishar, 2018;Daniyal et al, 2021;. Therefore, there is an urgent need to discover and develop new drugs for the treatment of BC, particularly for TNBC.…”

Section: Introductionmentioning

confidence: 99%

Machine Learning Enables Accurate and Rapid Prediction of Active Molecules Against Breast Cancer Cells

Zhao

Ling

et al. 2021

Front. Pharmacol.

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Breast cancer (BC) has surpassed lung cancer as the most frequently occurring cancer, and it is the leading cause of cancer-related death in women. Therefore, there is an urgent need to discover or design new drug candidates for BC treatment. In this study, we first collected a series of structurally diverse datasets consisting of 33,757 active and 21,152 inactive compounds for 13 breast cancer cell lines and one normal breast cell line commonly used in in vitro antiproliferative assays. Predictive models were then developed using five conventional machine learning algorithms, including naïve Bayesian, support vector machine, k-Nearest Neighbors, random forest, and extreme gradient boosting, as well as five deep learning algorithms, including deep neural networks, graph convolutional networks, graph attention network, message passing neural networks, and Attentive FP. A total of 476 single models and 112 fusion models were constructed based on three types of molecular representations including molecular descriptors, fingerprints, and graphs. The evaluation results demonstrate that the best model for each BC cell subtype can achieve high predictive accuracy for the test sets with AUC values of 0.689–0.993. Moreover, important structural fragments related to BC cell inhibition were identified and interpreted. To facilitate the use of the model, an online webserver called ChemBC (http://chembc.idruglab.cn/) and its local version software (https://github.com/idruglab/ChemBC) were developed to predict whether compounds have potential inhibitory activity against BC cells.

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“…Various studies have shown that mutations in oncogenes and tumor suppressors such as K-Ras and P53 play an important role in the drug resistance of cancer cells. These mutations can cause significant changes in associated cellular signaling pathways leading to attenuated apoptosis, enhanced expression of ABC family transporter, and enhanced DNA repair [100][101][102][103][104]. In addition, many important receptors involved in cell growth and proliferation, various components of the signaling pathways associated with them, and a large number of proteins involved in proliferation and apoptosis may undergo mutations leading to enhanced proliferation and drug resistance.…”

Section: Crispr/cas9 Gene Editing Applications In Overcoming Drug Res...mentioning

confidence: 99%

CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer

et al. 2022

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The CRISPR/Cas9 system is an RNA-based adaptive immune system in bacteria and archaea. Various studies have shown that it is possible to target a wide range of human genes and treat some human diseases, including cancers, by the CRISPR/Cas9 system. In fact, CRISPR/Cas9 gene editing is one of the most efficient genome manipulation techniques. Studies have shown that CRISPR/Cas9 technology, in addition to having the potential to be used as a new therapeutic approach in the treatment of cancers, can also be used to enhance the effectiveness of existing treatments. Undoubtedly, the issue of drug resistance is one of the main obstacles in the treatment of cancers. Cancer cells resist anticancer drugs by a variety of mechanisms, such as enhancing anticancer drugs efflux, enhancing DNA repair, enhancing stemness, and attenuating apoptosis. Mutations in some proteins of different cellular signaling pathways are associated with these events and drug resistance. Recent studies have shown that the CRISPR/Cas9 technique can be used to target important genes involved in these mechanisms, thereby increasing the effectiveness of anticancer drugs. In this review article, studies related to the applications of this technique in overcoming drug resistance in cancer cells will be reviewed. In addition, we will give a brief overview of the limitations of the CRISP/Cas9 gene-editing technique.

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Genetic Influences in Breast Cancer Drug Resistance

Cited by 12 publications

References 187 publications

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Machine Learning Enables Accurate and Rapid Prediction of Active Molecules Against Breast Cancer Cells

CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer

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