HER2 异质性与抗 HER2 抗体药物偶联物耐药性。

HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.

机构信息

Experimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos and IdISSC, Madrid, Spain.

Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.

出版信息

Breast Cancer Res. 2020 Jan 31;22(1):15. doi: 10.1186/s13058-020-1252-7.

DOI:10.1186/s13058-020-1252-7

PMID:32005279

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6995165/

Abstract

BACKGROUND

There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1).

METHODS

Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.

RESULTS

We describe results from clinical studies reporting the effect of anti-HER2 strategies particularly ADCs and their mechanistic effect. We review biological findings underlying HER2 heterogeneity and its implication in the development of novel anti-HER2 drugs including new ADCs in clinical development like trastuzumab deruxtecan (DS-8201).

CONCLUSIONS

We suggest potential mechanisms to optimize these compounds and their future clinical implementation.

摘要

背景

人们对 HER2 肿瘤内异质性产生了浓厚的兴趣，认为这是乳腺癌对抗 HER2 治疗（尤其是曲妥珠单抗-美坦新偶联物[T-DM1]）产生耐药性的原因。

方法

通过文献回顾的方法，我们讨论了乳腺癌中针对 HER2 靶向抗体药物偶联物（ADC）产生耐药的机制。

结果

我们描述了临床研究中报告的抗 HER2 策略（尤其是 ADC）及其作用机制的结果。我们回顾了 HER2 异质性的生物学基础及其对新型抗 HER2 药物（包括临床开发中的新型 ADC，如曲妥珠单抗 deruxtecan [DS-8201]）发展的影响。

结论

我们提出了优化这些化合物及其未来临床应用的潜在机制。

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本文引用的文献

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N Engl J Med. 2020 Feb 13;382(7):610-621. doi: 10.1056/NEJMoa1914510. Epub 2019 Dec 11.

TBCRC023: A Randomized Phase II Neoadjuvant Trial of Lapatinib Plus Trastuzumab Without Chemotherapy for 12 versus 24 Weeks in Patients with HER2-Positive Breast Cancer.

Clin Cancer Res. 2020 Feb 15;26(4):821-827. doi: 10.1158/1078-0432.CCR-19-0851. Epub 2019 Oct 29.

Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study.

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Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study.

Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29.

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Targeting the EGF/HER Ligand-Receptor System in Cancer.

Curr Pharm Des. 2016;22(39):5887-5898. doi: 10.2174/1381612822666160715132233.

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Upregulation of ER Signaling as an Adaptive Mechanism of Cell Survival in HER2-Positive Breast Tumors Treated with Anti-HER2 Therapy.

Clin Cancer Res. 2015 Sep 1;21(17):3995-4003. doi: 10.1158/1078-0432.CCR-14-2728. Epub 2015 May 26.

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HER2 异质性与抗 HER2 抗体药物偶联物耐药性。

HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.

机构信息

Experimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos and IdISSC, Madrid, Spain.

Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.

出版信息

Breast Cancer Res. 2020 Jan 31;22(1):15. doi: 10.1186/s13058-020-1252-7.

DOI:10.1186/s13058-020-1252-7

PMID:32005279

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6995165/

Abstract

BACKGROUND

METHODS

Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.

RESULTS

CONCLUSIONS

We suggest potential mechanisms to optimize these compounds and their future clinical implementation.

摘要

背景

人们对 HER2 肿瘤内异质性产生了浓厚的兴趣，认为这是乳腺癌对抗 HER2 治疗（尤其是曲妥珠单抗-美坦新偶联物[T-DM1]）产生耐药性的原因。

方法

通过文献回顾的方法，我们讨论了乳腺癌中针对 HER2 靶向抗体药物偶联物（ADC）产生耐药的机制。

结果

结论

我们提出了优化这些化合物及其未来临床应用的潜在机制。

HER2 异质性与抗 HER2 抗体药物偶联物耐药性。

HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.

机构信息

出版信息

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

背景

方法

结果

结论

相似文献

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HER2 异质性与抗 HER2 抗体药物偶联物耐药性。

HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.

机构信息

出版信息

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

背景

方法

结果

结论