Analysis of different <scp>HER</scp>‐2 mutations in breast cancer progression and drug resistance

Sun, Zhixin; Shi, Ying; Shen, Yan; Cao, Lulu; Zhang, Wenwen; Guan, Xiaoxiang

doi:10.1111/jcmm.12662

Cited by 53 publications

(45 citation statements)

References 115 publications

(186 reference statements)

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“…Cancer cells can become resistant to antibodies due to genetic mutations, leading to innate or acquired resistance towards the treatment, as seen for the use of Herceptin to treat HER2 positive breast cancers. [54,55] Additionally, the present study has shown enhanced cell kill compared to previous work where other carbohydrates have been used for selective cancer targeting. [13,15] More importantly, we have successfully increased levels of cell death with lower irradiation periods and radiation doses (29 mW/cm 2 ; 10.5 J/cm 2 for 6 minutes) to those reported previously (50 mW/cm 2 ; 90 J/cm 2 for 30 minutes).…”

Section: Discussionsupporting

confidence: 47%

Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles

Calavia

Chambrier

Cook

et al. 2018

Journal of Colloid and Interface Science

103

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Gold nanoparticles (AuNPs), which have been widely used for the delivery of photosensitizers for photodynamic therapy (PDT) of cancer, can be dispersed in aqueous solutions improving the delivery of the hydrophobic photosensitizer into the body. Furthermore, the large surface of AuNPs can be functionalized with a variety of ligands, including proteins, nucleic acids and carbohydrates, that allow selective targeting to cancer tissue. In this study, gold nanoparticles were functionalized with a mixed monolayer of a zinc phthalocyanine and a lactose derivative. For the first time, a carbohydrate was used with a dual purpose, as the stabilizing agent of the gold nanoparticles in aqueous solutions and as the targeting agent for breast cancer cells. The functionalization of the phthalocyanine-AuNPs with lactose led to the production of water-dispersible nanoparticles that are able to generate singlet oxygen and effect cell death upon irradiation. The targeting ability of lactose of the lactose-phthalocyanine functionalized AuNPs was studied in vitro towards the galectin-1 receptor on the surface of breast cancer cells. The targeting studies showed the exciting potential of lactose as a specific targeting agent for galactose-binding receptors overexpressed on breast cancer cells.

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Section: Discussionsupporting

confidence: 47%

Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles

Calavia

Chambrier

Cook

et al. 2018

Journal of Colloid and Interface Science

103

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“…22 It is interesting to note that ERBB2mut when accompanying ERBB2amp has been cited as a potential acquired resistance mechanism for patients with HER2-positive disease originally detected by IHC and/or FISH and currently progressing on standard anti-HER2 targeted therapies. 38 The most frequently altered genes in this series of ERBB2mut breast cancers included TP53 (49%) and PIK3CA (42%). This TP53 mutation frequency is higher than that published for primary breast cancer and the enrichment may reflect the fact that all the patients had stage IV disease at the time of sequencing 34 and that TP53 missense mutation is a negative prognostic factor for breast cancer.…”

Section: Original Articlementioning

confidence: 77%

“…It has been theorized that anti‐HER2 antibody therapeutics such as trastuzumab and pertuzumab may be useful in the treatment of ERBB2 mut tumors, especially when the mutation is within the ECD and causing enhanced dimerization of the HER2 and HER3 proteins . It is interesting to note that ERBB2 mut when accompanying ERBB2 amp has been cited as a potential acquired resistance mechanism for patients with HER2‐positive disease originally detected by IHC and/or FISH and currently progressing on standard anti‐HER2 targeted therapies …”

Section: Discussionmentioning

confidence: 99%

Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti‐HER2 targeted therapies

Ross

Gay²,

Wang

et al. 2016

Cancer

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BACKGROUND: Activating, nonamplification ERBB2 mutations (ERBB2mut) are not detected by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but are detected by DNA sequencing and may predict clinical responses to human epidermal growth factor receptor (HER2)-targeted therapy. The authors queried 5605 advanced/metastatic breast cancers (mBC) to uncover the frequency of ERBB2mut genomic alterations. Clinical responses to anti-HER2 therapeutics were identified. METHODS: DNA was extracted from 40 mm of formalin-fixed paraffin-embedded (FFPE) sections. Comprehensive genomic profiling (CGP) was used to evaluate up to 315 genes (5923 mean coverage depth). Results were analyzed for base substitutions, short indels, copy number changes, and selected rearrangements. RESULTS: Of 5605 cases, 698 (12.5%) featured ERBB2 alterations, including 596 (10.6%) ERBB2 amplifications (ERBB2amp) and 138 (2.4%) ERBB2mut; 38 cases (0.7%) had co-occurring ERBB2amp and ERBB2mut. ERBB2mut predominantly affected the kinase (124 cases; 90%) or extracellular (15 cases; 11%) domains. Both primary BC (52 cases; 38%) and metastatic site biopsies (86 cases; 62%) were found to harbor ERBB2mut, which were distributed across carcinoma not otherwise specified (NOS) (69 cases; 50%), invasive ductal carcinoma (IDC) (40 cases; 29%), invasive lobular carcinoma (ILC) (27 cases; 20%), and mucinous mBC (2 cases; 1%). Genes commonly coaltered with ERBB2 were tumor protein 53 (TP53) (49%); phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (42%); cadherin 1, type 1 (CDH1) (37%); MYC (17%); and cyclin D1 protein (CCND1) (16%). CDH1 mutations were enriched in ERBB2mut mBC (P<0.0006) and associated with recurrent mBC. Selected patients with ERBB2mut, without ERBB2amp, who responded to anti-HER2 targeted therapies are presented herein. CONCLUSIONS: Within this large series, 1.8% of cases harbored ERBB2mut, which are undetectable by standard-of-care IHC or FISH tests. Metastatic BC driven by ERBB2mut respond to anti-HER2 targeted therapies, and expanding clinical trials designed to detect ERBB2mut by CGP and optimize targeted treatments are warranted. Cancer 2016;122:2654-62. V C 2016 American Cancer Society.KEYWORDS: breast cancer, comprehensive genomic profiling, ERBB2, human epidermal growth factor receptor 2 [HER2]/neu, nextgeneration sequencing, short variants. INTRODUCTIONThe ERBB2 gene encodes a transmembrane tyrosine kinase receptor that is a member of the epidermal growth factor receptor/ human epidermal growth factor receptor (HER) family of proteins.1 ERBB2 gene amplification has been identified in 10% to 34% of invasive breast cancers, is associated with HER2 (p185 neu) protein overexpression, and has been associated with increased cell proliferation, cell motility, tumor invasiveness, progressive regional and distant metastases, accelerated angiogenesis, and reduced apoptosis.2-4 ERBB2-driven breast cancer is more frequently associated with higher histologic grade, is more often negative for estrogen receptor (ER) and p...

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“…Recently, data from preclinical and clinical studies have attributed somatic mutations in HER2, a role in the constitutive expression [31][32][33] or differential regulation of HER2 that leads to resistance (primary or acquired) to anti-HER2 therapy and endocrine therapy [4,6,10,[34][35][36]. Such mutations therefore undermine the clinical benefits of HER2-targeted treatment in HER2-positive breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer

Gaibar

Beltrán

Romero‐Lorca

et al. 2020

Journal of Oncology

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In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.

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Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

Cited by 53 publications

References 115 publications

Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles

Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles

Nonamplification ERBB2 genomic alterations in 5605 cases of recurrent and metastatic breast cancer: An emerging opportunity for anti‐HER2 targeted therapies

Somatic Mutations in HER2 and Implications for Current Treatment Paradigms in HER2-Positive Breast Cancer

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