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HER3 在癌症中的作用：从基础研究到临床应用。

HER3 in cancer: from the bench to the bedside.

机构信息

Instituto de Biología Molecular y Celular del Cáncer, CSIC, IBSAL and CIBERONC, Campus Miguel de Unamuno, 37007, Salamanca, Spain.

Hospital Clínico San Carlos and CIBERONC, 28040, Madrid, Spain.

出版信息

J Exp Clin Cancer Res. 2022 Oct 21;41(1):310. doi: 10.1186/s13046-022-02515-x.

DOI:10.1186/s13046-022-02515-x
PMID:36271429
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9585794/
Abstract

The HER3 protein, that belongs to the ErbB/HER receptor tyrosine kinase (RTK) family, is expressed in several types of tumors. That fact, together with the role of HER3 in promoting cell proliferation, implicate that targeting HER3 may have therapeutic relevance. Furthermore, expression and activation of HER3 has been linked to resistance to drugs that target other HER receptors such as agents that act on EGFR or HER2. In addition, HER3 has been associated to resistance to some chemotherapeutic drugs. Because of those circumstances, efforts to develop and test agents targeting HER3 have been carried out. Two types of agents targeting HER3 have been developed. The most abundant are antibodies or engineered antibody derivatives that specifically recognize the extracellular region of HER3. In addition, the use of aptamers specifically interacting with HER3, vaccines or HER3-targeting siRNAs have also been developed. Here we discuss the state of the art of the preclinical and clinical development of drugs aimed at targeting HER3 with therapeutic purposes.

摘要

HER3 蛋白属于表皮生长因子受体家族（ErbB/HER receptor tyrosine kinase，RTK），在多种类型的肿瘤中表达。这一事实，以及 HER3 在促进细胞增殖中的作用，表明针对 HER3 可能具有治疗相关性。此外，HER3 的表达和激活与对其他 HER 受体靶向药物的耐药性有关，如针对 EGFR 或 HER2 的药物。此外，HER3 与一些化疗药物的耐药性有关。由于这些情况，已经进行了开发和测试针对 HER3 的药物的努力。已经开发了两种针对 HER3 的药物类型。最常见的是抗体或工程抗体衍生物，它们特异性地识别 HER3 的细胞外区域。此外，还开发了与 HER3 特异性相互作用的适体、疫苗或 HER3 靶向 siRNA。在这里，我们讨论了以治疗为目的针对 HER3 的药物的临床前和临床开发的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e9/9585794/85bb64ecf361/13046_2022_2515_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e9/9585794/31ce2f1b8bb4/13046_2022_2515_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e9/9585794/30a0fbdcf184/13046_2022_2515_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e9/9585794/85bb64ecf361/13046_2022_2515_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e9/9585794/31ce2f1b8bb4/13046_2022_2515_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e9/9585794/30a0fbdcf184/13046_2022_2515_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24e9/9585794/85bb64ecf361/13046_2022_2515_Fig3_HTML.jpg

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HER3 in cancer: from the bench to the bedside.

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[5]
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[7]
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Clin Cancer Res. 2025-5-1

[8]
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[9]
DB-1310, a HER3-targeting antibody-drug conjugate, has synergistic anti-tumor activity with trastuzumab in HER2- and HER3-expressing breast cancer.

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[10]
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本文引用的文献

[1]
Triple Targeting of HER Receptors Overcomes Heregulin-mediated Resistance to EGFR Blockade in Colorectal Cancer.

Mol Cancer Ther. 2022-5-4

[2]
Her3-specific affibody mediated tumor targeting delivery of ICG enhanced the photothermal therapy against Her3-positive tumors.

Int J Pharm. 2022-4-5

[3]
Zenocutuzumab, a HER2xHER3 Bispecific Antibody, Is Effective Therapy for Tumors Driven by NRG1 Gene Rearrangements.

Cancer Discov. 2022-5-2

[4]
First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies.

Invest New Drugs. 2022-6

[5]
Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers.

Cell Rep. 2022-2-1

[6]
Differential tumor inhibitory effects induced by HER3 extracellular subdomain-specific mouse monoclonal antibodies.

Cancer Chemother Pharmacol. 2022-3

[7]
Enhancing Radioiodine Incorporation in -Mutant, Radioiodine-Refractory Thyroid Cancers with Vemurafenib and the Anti-ErbB3 Monoclonal Antibody CDX-3379: Results of a Pilot Clinical Trial.

Thyroid. 2022-3

[8]
Patritumab Deruxtecan: Paving the Way for EGFR-TKI-Resistant NSCLC.

Cancer Discov. 2022-1

[9]
HER3 Augmentation via Blockade of EGFR/AKT Signaling Enhances Anticancer Activity of HER3-Targeting Patritumab Deruxtecan in EGFR-Mutated Non-Small Cell Lung Cancer.

Clin Cancer Res. 2022-1-15

[10]
Fc-comprising scDb-based trivalent, bispecific T-cell engagers for selective killing of HER3-expressing cancer cells independent of cytokine release.

J Immunother Cancer. 2021-11

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