Targeted therapeutic options and future perspectives for HER2-positive breast cancer

Wang, Jiani; Xu, Binghe

doi:10.1038/s41392-019-0069-2

Cited by 298 publications

(271 citation statements)

References 337 publications

(452 reference statements)

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“…In short, a considerable number of preclinical studies have been performed and equally a significant number is ongoing in different parts of the world. Concise reviews on the use of these models have been mentioned by Tong et al and Wang and Xu [184,185]. Although these models serve as the best option for studying and analyzing the role of different molecules in progression and treatment of breast cancer, however, neither of them could actually represent the humanized model of the disease.…”

Section: Preclinical Modelsmentioning

confidence: 99%

A three layered histone epigenetics in breast cancer metastasis

2020

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Thanks to the advancement in science and technology and a significant number of cancer research programs being carried out throughout the world, the prevention, prognosis and treatment of breast cancer are improving with a positive and steady pace. However, a stern thoughtful attention is required for the metastatic breast cancer casesthe deadliest of all types of breast cancer, with a character of relapse even when treated. In an effort to explore the less travelled avenues, we summarize here studies underlying the aspects of histone epigenetics in breast cancer metastasis. Authoritative reviews on breast cancer epigenetics are already available; however, there is an urgent need to focus on the epigenetics involved in metastatic character of this cancer. Here we put forward a comprehensive review on how different layers of histone epigenetics comprising of histone chaperones, histone variants and histone modifications interplay to create breast cancer metastasis landscape. Finally, we propose a hypothesis of integrating histone-epigenetic factors as biomarkers that encompass different breast cancer subtypes and hence could be exploited as a target of larger population.

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Section: Preclinical Modelsmentioning

confidence: 99%

A three layered histone epigenetics in breast cancer metastasis

2020

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“…Targeted anti-HER2 drugs have been used in HER2+ breast cancer patients for several decades. Both early and late stage disease patients have benefitted from this approach, which is widely reviewed elsewhere [11,16,[21][22][23][24] . Anti-HER2 drugs include trastuzumab, pertuzumab, margetuximab, trastuzumab trastuzumab emtansine DM1 (T-DM1), and lapatinib.…”

Section: Her2 Specific Targeted Therapeuticsmentioning

confidence: 99%

Targeted lapatinib anti-HER2/ErbB2 therapy resistance in breast cancer: opportunities to overcome a difficult problem

Wahdan-Alaswad¹,

Thor²

2020

CDR

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Approximately 20% of invasive breast cancers have upregulation/gene amplification of the oncogene human epidermal growth factor receptor-2 (HER2/ErbB2). Of these, some also express steroid receptors (the so-called Luminal B subtype), whereas others do not (the HER2 subtype). HER2 abnormal breast cancers are associated with a worse prognosis, chemotherapy resistance, and sensitivity to selected anti-HER2 targeted therapeutics. Transcriptional data from over 3000 invasive breast cancers suggest that this approach is overly simplistic; rather, the upregulation of HER2 expression resulting from gene amplification is a driver event that causes major transcriptional changes involving numerous genes and pathways in breast cancer cells. Most notably, this includes a shift from estrogenic dependence to regulatory controls driven by other nuclear receptors, particularly the androgen receptor. We discuss members of the HER receptor tyrosine kinase family, heterodimer formation, and downstream signaling, with a focus on HER2 associated pathology in breast carcinogenesis. The development and application of anti-HER2 drugs, including selected clinical trials, are discussed. In light of the many excellent reviews in the clinical literature, our emphasis is on recently developed and successful strategies to overcome targeted therapy resistance. These include combining anti-HER2 agents with programmed cell death-1 ligand or cyclin-dependent kinase 4/6 inhibitors, targeting crosstalk between HER2 and other nuclear receptors, lipid/cholesterol synthesis to inhibit receptor tyrosine kinase activation, and metformin, a broadly inhibitory drug. We seek to facilitate a better understanding of new approaches to overcome anti-HER2 drug resistance and encourage exploration of two other therapeutic interventions that may be clinically useful for HER+ invasive breast cancer patients.A robust and reliable determination of hormone receptor and HER2 "status" in newly diagnosed breast cancer is more difficult to achieve than it may seem. Some of this is due to clinical and surgical nuances of individual patient tumors, as well as the distance and time required for transportation of the biopsy, examination, and processing by pathology. Clinical teams should adhere to the most recent widely accepted practice guidelines, developed by a working group and codified by the College of American Pathologists and the American Society of Clinical Oncology (www.asco.org/breast-cancer-guidelines) [13] . These recommendations include the use of FDA approved reagents, test, and reporting methodology. Testing must be performed in a clinical laboratory improvement amendments-certified laboratory, using appropriate controls and validated assays. Each of these assays requires a pathologist to perform a semi-quantitative analysis of the cancer sample using evidence-based interpretive guidelines and visual microscopy [14] .

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“…The nude mice were injected subcutaneously in the anks with 5 × 10 6 SK-OV-3, HCT116 or MDA-MB-231 cells respectively. In the exosome-delivered miR-HER2-E1 treatment, mice with tumors having an average volume of 90 mm 3…”

Section: Immunoblotting Assaymentioning

confidence: 99%

“…HER2 is a member of the human epidermal growth factor receptor family [1][2][3]. The HER2 protein is expressed at high levels on the surface of human breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enhanced antitumor activity

Wang

Zhou

Zou

et al. 2020

Preprint

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Background: Exosomes are small, cellular membrane-derived vesicles with a diameter of 50-150 nm. Exosomes are considered ideal drug delivery systems with a wide range of applications in various diseases, including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains challenging. H uman epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase, and its overexpression is usually associated with cell survival and tumor progression in various cancers. In this study, we aim to develop novel exosomes with dual HER2-targeting ability as a nanoparticle delivery vehicle to enhance antitumor efficacy in vivo . Results: Here, we report the generation of two kinds of exosomes carrying miRNAs designed to block HER2 synthesis and consequently kill tumor cells. 293-miR-HER2 exosomes package and deliver designed miRNAs to cells to block HER2 synthesis. These exosomes kill cancer cells dependent on HER2 for survival but do not affect cells that lack HER2 or that are engineered to express HER2 but are not dependent on it for survival. In contrast, 293-miR-XS-HER2 exosomes carry an additional peptide, which enables them to adhere to HER2 on the surface of cancer cells. Consequently, these exosomes preferentially enter and kill cells with surface expression of HER2. 293-miR-XS-HER2 exosomes are significantly more effective than the 293-miR-HER2 exosomes in shrinking HER2-positive tumors implanted in mice. Conclusions: Collectively, as novel antitumor drug delivery vehicles, HER2 dual-targeting exosomes exhibit increased target-specific delivery efficiency and can be further utilized to develop new nanoparticle-based targeted therapies.

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Targeted therapeutic options and future perspectives for HER2-positive breast cancer

Cited by 298 publications

References 337 publications

A three layered histone epigenetics in breast cancer metastasis

A three layered histone epigenetics in breast cancer metastasis

Targeted lapatinib anti-HER2/ErbB2 therapy resistance in breast cancer: opportunities to overcome a difficult problem

Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enhanced antitumor activity

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