Overcoming doxorubicin resistance of cancer cells by Cas9-mediated gene disruption

Ha, Jong Seong; Byun, Ji Young; Ahn, Dae‐Ro

doi:10.1038/srep22847

Cited by 41 publications

(44 citation statements)

References 29 publications

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“…MCF‐7/ADR cells were treated with doxorubicin after disruption of MDR1 by Cas9‐sgRNA, and possible drug sensitivity recovery was examined. The potency of doxorubicin was enhanced in the cells treated with CRISPR/Cas9 expression construction using a proper delivery platform 80. This result indicates that disruption of this drug resistance‐related gene can be considered to overcome MDR in cancer cells.…”

Section: How Crispr/cas9 Overcomes Drug Resistancementioning

confidence: 91%

“…Based on the strategy described by Ha et al,80 after identification of the specific expression of genes related to drug resistance mentioned above, they could be edited by the CRISPR/Cas9 system to recover drug sensitivity, which makes downregulation of efflux‐mediated chemotherapy resistance available. This is a promising way to overcome MDR of cancer cells.…”

Section: How Crispr/cas9 Overcomes Drug Resistancementioning

confidence: 99%

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Application of the CRISPR/Cas9 System to Drug Resistance in Breast Cancer

Chen

Zhang

2018

Advanced Science

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Clinical evidence indicates that drug resistance is a great obstacle in breast cancer therapy. It renders the disease uncontrollable and causes high mortality. Multiple mechanisms contribute to the development of drug resistance, but the underlying cause is usually a shift in the genetic composition of tumor cells. It is increasingly feasible to engineer the genome with the clustered regularly interspaced short palindromic repeats (CRISPR)/associated (Cas)9 technology recently developed, which might be advantageous in overcoming drug resistance. This article discusses how the CRISPR/Cas9 system might revert resistance gene mutations and identify potential resistance targets in drug‐resistant breast cancer. In addition, the challenges that impede the clinical applicability of this technology and highlight the CRISPR/Cas9 systems are presented. The CRISPR/Cas9 system is poised to play an important role in preventing drug resistance in breast cancer therapy and will become an essential tool for personalized medicine.

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Section: How Crispr/cas9 Overcomes Drug Resistancementioning

confidence: 91%

Section: How Crispr/cas9 Overcomes Drug Resistancementioning

confidence: 99%

Application of the CRISPR/Cas9 System to Drug Resistance in Breast Cancer

Chen

Zhang

2018

Advanced Science

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“…Five additional articles published between 2016 and 2018 applied a similar approach to knockout ABCB1/MDR1in various cell lines. These investigated if the knockout of ABCB1 could reverse resistance in human cancer derived cell lines (Ha et al, 2016;Liu et al, 2016;Yang et al, 2016b;Takahashi et al, 2017;Norouzi-Barough et al, 2018). As expected, these studies showed decreased ABCB1/MDR1 mRNA or protein expression levels and increased intracellular accumulation, or increased sensitivity in the MDR1 knockout cells using MDR1 substrates such as rhodamine 123, doxorubicin, and/or carfilzomib.…”

Section: Drug Transportersmentioning

confidence: 99%

CRISPR-Cas9: A New Addition to the Drug Metabolism and Disposition Tool Box

et al. 2018

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Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 9 (Cas9), i.e., CRISPR-Cas9, has been extensively used as a gene-editing technology during recent years. Unlike earlier technologies for gene editing or gene knockdown, such as zinc finger nucleases and RNA interference, CRISPR-Cas9 is comparably easy to use, affordable, and versatile. Recently, CRISPR-Cas9 has been applied in studies of drug absorption, distribution, metabolism, and excretion (ADME) and for ADME model generation. To date, about 50 papers have been published describing in vitro or in vivo CRISPR-Cas9 gene editing of and-related genes. Twenty of these papers describe gene editing of clinically relevant genes, such as ATP-binding cassette drug transporters and cytochrome P450 drug-metabolizing enzymes. With CRISPR-Cas9, the ADME tool box has been substantially expanded. This new technology allows us to develop better and more predictive in vitro and in vivo ADME models and map previously underexplored genes and gene families. In this mini-review, we give an overview of the CRISPR-Cas9 technology and summarize recent applications of CRISPR-Cas9 within the ADME field. We also speculate about future applications of CRISPR-Cas9 in ADME research.

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“…This approach has already been applied in EFGR mutant lung cancer and osteosarcomas, though not in TNBC . CRISPR/Cas9 was engineered with a gRNA to target the md1 gene that codes for a drug efflux pump responsible for a prominent mechanism in cells that become drug resistant . Three Cas9/gRNA delivery methods were explored (Cas9/gRNA plasmid delivered by the protein transduction domain TAT, Cas9 Protein/gRNA complex delivered by Lipofectamine, and Cas9/gRNA complex delivered by cell penetration peptide) and yielded similar gene and protein disruption between 50–60% in MCF7 breast cancer cells.…”

Section: Crispr Technology For Breast Cancer Therapymentioning

confidence: 99%

CRISPR Technology for Breast Cancer: Diagnostics, Modeling, and Therapy

Mintz

Gao

et al. 2018

Adv. Biosys.

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Molecularly, breast cancer represents a highly heterogenous family of neoplastic disorders, with substantial interpatient variations regarding genetic mutations, cell composition, transcriptional profiles, and treatment response. Consequently, there is an increasing demand for alternative diagnostic approaches aimed at the molecular annotation of the disease on a patient‐by‐patient basis and the design of more personalized treatments. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated (Cas) technology enables the development of such novel approaches. For instance, in diagnostics, the use of the RNA‐specific C2c2 system allows ultrasensitive nucleic acid detection and could be used to characterize the mutational repertoire and transcriptional breast cancer signatures. In disease modeling, CRISPR/Cas9 technology can be applied to selectively engineer oncogenes and tumor‐suppressor genes involved in disease pathogenesis. In treatment, CRISPR/Cas9 can be used to develop gene‐therapy, while its catalytically‐dead variant (dCas9) can be applied to reprogram the epigenetic landscape of malignant cells. As immunotherapy becomes increasingly prominent in cancer treatment, CRISPR/Cas9 can engineer the immune cells to redirect them against cancer cells and potentiate antitumor immune responses. In this review, CRISPR strategies for the advancement of breast cancer diagnostics, modeling, and treatment are highlighted, culminating in a perspective on developing a precision medicine‐based approach against breast cancer.

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Overcoming doxorubicin resistance of cancer cells by Cas9-mediated gene disruption

Cited by 41 publications

References 29 publications

Application of the CRISPR/Cas9 System to Drug Resistance in Breast Cancer

Application of the CRISPR/Cas9 System to Drug Resistance in Breast Cancer

CRISPR-Cas9: A New Addition to the Drug Metabolism and Disposition Tool Box

CRISPR Technology for Breast Cancer: Diagnostics, Modeling, and Therapy

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