CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation

Liu, Bin; Arguello, Olivia Adaly Diaz; Deng, Chao; Chen, Siwei; Saber, Aly; Haisma, Hidde J.

doi:10.1371/journal.pone.0232985

Cited by 18 publications

(10 citation statements)

References 32 publications

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“…They found that CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib could significantly improve the therapeutic effect of sunitinib. Interestingly, the loss of EGFR eventually induced resistance to SAHA and cisplatin ( 156 ). Several studies have also shown that the EGFR status is associated with drug resistance in cancer, which suggests that EGFR knockout RC21 cells could be a cisplatin-resistant cell model.…”

Section: Transgenic Drug Resistance Modelsmentioning

confidence: 99%

Advances in Renal Cell Carcinoma Drug Resistance Models

Xiang

Zheng²,

Zhong³

et al. 2022

Front. Oncol.

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Renal cell carcinoma (RCC) is the most common form of kidney cancer. Systemic therapy is the preferred method to eliminate residual cancer cells after surgery and prolong the survival of patients with inoperable RCC. A variety of molecular targeted and immunological therapies have been developed to improve the survival rate and prognosis of RCC patients based on their chemotherapy-resistant properties. However, owing to tumor heterogeneity and drug resistance, targeted and immunological therapies lack complete and durable anti-tumor responses; therefore, understanding the mechanisms of systemic therapy resistance and improving clinical curative effects in the treatment of RCC remain challenging. In vitro models with traditional RCC cell lines or primary cell culture, as well as in vivo models with cell or patient-derived xenografts, are used to explore the drug resistance mechanisms of RCC and screen new targeted therapeutic drugs. Here, we review the established methods and applications of in vivo and in vitro RCC drug resistance models, with the aim of improving our understanding of its resistance mechanisms, increasing the efficacy of combination medications, and providing a theoretical foundation for the development and application of new drugs, drug screening, and treatment guidelines for RCC patients.

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Section: Transgenic Drug Resistance Modelsmentioning

confidence: 99%

Advances in Renal Cell Carcinoma Drug Resistance Models

Xiang

Zheng²,

Zhong³

et al. 2022

Front. Oncol.

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“…Liu et al used CRISPR/Cas9 technology to create renal cell carcinoma (RCC) cell lines with EGFR knockout, which significantly inhibited cancer cell proliferation and induced cell arrest in the G2/M phase. However, knocking out EGFR resulted in high ERK expression, but the authors discovered that ERK and Akt could be inhibited by Sunitinib (a multi-targeted TKI) in combination ( Liu et al, 2020 ), suggesting that CRISPR mediated knockout of drug resistance genes may be a promising option for future disease treatment.…”

Section: Principles Of Multidrug Resistance In Nsclc Reversed By Cris...mentioning

confidence: 99%

Application and Prospect of CRISPR/Cas9 Technology in Reversing Drug Resistance of Non-Small Cell Lung Cancer

et al. 2022

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Cancer drug resistance has always been a major factor affecting the treatment of non-small cell lung cancer, which reduces the quality of life of patients. The clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology, as an efficient and convenient new gene-editing technology, has provided a lot of help to the clinic and accelerated the research of cancer and drug resistance. In this review, we introduce the mechanisms of drug resistance in non-small cell lung cancer (NSCLC), discuss how the CRISPR/Cas9 system can reverse multidrug resistance in NSCLC, and focus on drug resistance gene mutations. To improve the prognosis of NSCLC patients and further improve patients’ quality of life, it is necessary to utilize the CRISPR/Cas9 system in systematic research on cancer drug resistance.

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“…In addition to it is overexpression in breast cancer. [9] FDA approved several drugs targeting EGFR such as sorafenib I [13], sunitinib II [14], erlotinib [15] III (Figure 1), lapatinib [16], gefitinib [17] and osimertinib [18]. Most of these developed drugs usually binds to ATP active site of EGFR-TK.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents

Shoman

Soltan

Nagaoka

et al. 2021

Journal of advanced Biomedical and Pharmaceutical Sciences

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A series of novel 1,5-diarylpyrazole carboxamide derivatives was designed and synthesized. All the synthesized compounds were biologically evaluated for their in vitro cytotoxic activities against a panel of five cancer cell lines namely, DLD, Hela, K-562, SUIT and HepG-2. The results revealed that compound 5c exhibited the most prominent cytotoxic effect against four tested cell lines with growth inhibition percentages ranged from 75.95 to 123 % and IC50 values of 17.20 and 21.20 μM comparable to that of daunorubicin as a control drug (IC50 values of 13.30 and 22 μM) against K-562 and Hep-G2 cell lines, respectively. Molecular docking study suggested the ability of the tested compounds to inhibit EGFR-TK. Data showed that 5c possess the ability to bind to erlotinib binding site forming a stable complex with energy scores -7.73 compared to -7.63 for erlotinib. It potentially forms three hydrogen bonds with LYS 721 and GLU 638 residues. Data suggests that compound 5c is a promising lead in the design of further EGFR inhibitors.

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CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation

Cited by 18 publications

References 32 publications

Advances in Renal Cell Carcinoma Drug Resistance Models

Advances in Renal Cell Carcinoma Drug Resistance Models

Application and Prospect of CRISPR/Cas9 Technology in Reversing Drug Resistance of Non-Small Cell Lung Cancer

Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel 1,5-Diarylpyrazole Carboxamide Derivatives as Antiproliferative Agents

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