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用于理解乳腺癌患者耐药机制的赫赛汀耐药数据库。

Herceptin resistance database for understanding mechanism of resistance in breast cancer patients.

作者信息

Ahmad Sahil, Gupta Sudheer, Kumar Rahul, Varshney Grish C, Raghava Gajendra P S

机构信息

1] CSIR-Institute of Microbial Technology Chandigarh, India [2].

CSIR-Institute of Microbial Technology Chandigarh, India.

出版信息

Sci Rep. 2014 Mar 27;4:4483. doi: 10.1038/srep04483.

DOI:10.1038/srep04483
PMID:24670875
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3967150/
Abstract

Monoclonal antibody Trastuzumab/Herceptin is considered as frontline therapy for Her2-positive breast cancer patients. However, it is not effective against several patients due to acquired or de novo resistance. In last one decade, several assays have been performed to understand the mechanism of Herceptin resistance with/without supplementary drugs. This manuscript describes a database HerceptinR, developed for understanding the mechanism of resistance at genetic level. HerceptinR maintains information about 2500 assays performed against various breast cancer cell lines (BCCs), for improving sensitivity of Herceptin with or without supplementary drugs. In order to understand Herceptin resistance at genetic level, we integrated genomic data of BCCs that include expression, mutations and copy number variations in different cell lines. HerceptinR will play a vital role in i) designing biomarkers to identify patients eligible for Herceptin treatment and ii) identification of appropriate supplementary drug for a particular patient. HerceptinR is available at http://crdd.osdd.net/raghava/herceptinr/.

摘要

单克隆抗体曲妥珠单抗/赫赛汀被视为Her2阳性乳腺癌患者的一线治疗药物。然而,由于获得性或原发性耐药,它对部分患者无效。在过去十年中,已经进行了多项试验,以了解使用或不使用辅助药物时赫赛汀耐药的机制。本手稿描述了一个名为HerceptinR的数据库,该数据库旨在从基因层面了解耐药机制。HerceptinR保存了针对各种乳腺癌细胞系(BCC)进行的2500项试验的信息,用于提高使用或不使用辅助药物时赫赛汀的敏感性。为了从基因层面了解赫赛汀耐药性,我们整合了乳腺癌细胞系的基因组数据,这些数据包括不同细胞系中的表达、突变和拷贝数变异。HerceptinR将在以下方面发挥重要作用:i)设计生物标志物以识别适合接受赫赛汀治疗的患者,ii)为特定患者识别合适的辅助药物。可通过http://crdd.osdd.net/raghava/herceptinr/访问HerceptinR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef26/3967150/1bbe759ad02e/srep04483-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef26/3967150/06ccdc28c91d/srep04483-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef26/3967150/f5ed53bde8c9/srep04483-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef26/3967150/1bbe759ad02e/srep04483-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef26/3967150/06ccdc28c91d/srep04483-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef26/3967150/f5ed53bde8c9/srep04483-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef26/3967150/1bbe759ad02e/srep04483-f3.jpg

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PTEN, Akt, MAPK, p53 and p95 expression to predict trastuzumab resistance in HER2 positive breast cancer.通过PTEN、Akt、MAPK、p53和p95表达来预测HER2阳性乳腺癌中曲妥珠单抗耐药性。
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The predictive role of phosphatase and tensin homolog (PTEN) loss, phosphoinositol-3 (PI3) kinase (PIK3CA) mutation, and PI3K pathway activation in sensitivity to trastuzumab in HER2-positive breast cancer: a meta-analysis.
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Discov Oncol. 2024 Aug 29;15(1):385. doi: 10.1007/s12672-024-01270-z.
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miR-770-5p-induced cellular switch to sensitize trastuzumab resistant breast cancer cells targeting HER2/EGFR/IGF1R bidirectional crosstalk.miR-770-5p诱导细胞转变,使靶向HER2/EGFR/IGF1R双向串扰的曲妥珠单抗耐药乳腺癌细胞致敏。
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