Dual Targeting of ERBB2/ERBB3 for the Treatment of SLC3A2-NRG1–Mediated Lung Cancer

Shin, Dong Hoon; Jo, Jeong Yeon; Han, Ji‐Youn

doi:10.1158/1535-7163.mct-17-1178

Cited by 31 publications

(22 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As NRG1 alterations activate the ERBB2/ERBB3 signaling pathway, targeted treatment with inhibitors of this pathway is an appealing therapeutic strategy. Dual targeting of ERBB2 and ERBB3 has also been evaluated in preclinical models (22,23). Afatinib, a pan-ERBB inhibitor, was successfully utilized in this manner, and several patients with tumor harboring an NRG1 fusion achieved durable benefit with afatinib (11)(12)(13).…”

Section: Discussionmentioning

confidence: 99%

Detection of NRG1 Gene Fusions in Solid Tumors

Jonna

Feldman

Swensen

et al. 2019

Clinical Cancer Research

171

190

View full text Add to dashboard Cite

Purpose: NRG1 gene fusions are rare but potentially actionable oncogenic drivers that are present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners. Experimental Design: Tumor specimens submitted for molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA)-certified genomics laboratory and that underwent fusion testing by anchored multiplex PCR for targeted RNA sequencing were retrospectively identified. The overall and tumor-specific incidence was noted, as was the specific fusion partner. Results: Out of 21,858 tumor specimens profiled from September 2015 to December 2018, 41 cases (0.2%) harbored an NRG1 fusion. Multiple fusion partners were identified. Fusion events were seen across tumor types. The greatest incidence was in non-small cell lung cancer (NSCLC, 25), though this represented only 0.3% of NSCLC cases tested. Other tumor types harboring an NRG1 fusion included gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, pancreatic cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer. Conclusions: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner. See related commentary by Dimou and Camidge, p. 4865

show abstract

Section: Discussionmentioning

confidence: 99%

Detection of NRG1 Gene Fusions in Solid Tumors

Jonna

Feldman

Swensen

et al. 2019

Clinical Cancer Research

171

190

View full text Add to dashboard Cite

show abstract

“…It should be noted that, in contrast to aforementioned case reports of afatinib, some of these patients experienced progressive disease following afatinib monotherapy (Table 1). Notably, an in vitro study using afatinib, pertuzumab (anti-ERBB2 mAb), and lumretuzumab against an SLC3A2-NRG1 fusion model reported that the combination treatment with two mAbs or the combination treatment of one of the drugs plus taxol was more effective than each of the single agents alone (45). These in vitro studies will be important to evaluate the effectiveness of potential treatment strategies, although the results should be confirmed in clinical settings.…”

Section: Nrg1 Fusionsmentioning

confidence: 99%

Emerging oncogenic fusions other than ALK, ROS1, RET, and NTRK in NSCLC and the role of fusions as resistance mechanisms to targeted therapy

Suda¹,

Mitsudomi²

2020

Transl Lung Cancer Res

View full text Add to dashboard Cite

Recent evidence has shown that gene fusions caused by chromosomal rearrangements are frequent events in the initiation and during progression of solid tumors, including non-small cell lung cancers (NSCLCs). Since the discoveries of ALK and ROS1 fusions in 2007 and the subsequent successes of pharmacological targeting for these fusions, numerous efforts have identified additional oncogenic driver fusions in NSCLCs, especially in lung adenocarcinomas. In this review, we will summarize recent advances in this field focusing on novel oncogenic fusions other than ALK, ROS1, NTRK, and RET fusions, which are summarized in other articles in this thematic issue. These novel gene fusions include neuregulin-1 (NRG1) fusions, MET fusions, fusion genes involving fibroblast growth factor receptor (FGFR) family members, EGFR fusions, and other rare fusions. In addition, evidence has suggested that acquisition of gene fusions by cancer cells can be a molecular mechanism of acquired resistance to targeted therapies. Most of the current data are from analyses of resistance mechanisms to EGFR tyrosine kinase inhibitors in lung cancers with oncogenic EGFR mutations. However, a few recent studies suggest that gene fusions can also be a resistance mechanism to ALK-tyrosine kinase inhibitors in lung cancers with oncogenic ALK fusions. Detection, validation, and pharmacological inhibition of these fusion genes are becoming more important in the treatment of NSCLC patients.

show abstract

“…Promote cell mitosis, regulate cell proliferation, differentiation, migration and tumor formation[52,53]. ERBB2 is overexpressed to varying degrees in various malignancies such as breast cancer[54], ovarian cancer[55], non-small cell lung cancer[56], gastric cancer[57], and etc.. ERBB3 / ERBB2 dimer is the most active ERBB dimer in ERBB dimer, which can activate PI3K/AKT Jak/Stat and other signaling pathways, regulate cell proliferation, differentiation, migration and other activities[58].ERBB3 is closely related to the occurrence and development of various tumors. Abnormal activation and overexpression of the HER3 gene can be seen in malignant tumors such as breast cancer[59], gastric cancer[60], ovarian cancer[61], prostate cancer[62], and etc.. After binding ERBB4 with ligands (neurodifferentiation factor heparin binding epidermal growth factor, etc.…”

mentioning

confidence: 99%

The Expression and Prognostic Values of Epidermal Growth Factor Receptor Family in Glioma

Huo

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Epidermal growth factor receptor (EGFR) family belongs to the transmembrane protein receptor of tyrosine kinase I subfamily, including 4 members, they are EGFR/ERBB1, ERBB2, ERBB3, ERBB4. The EGFR family is closely related to the occurrence and development of a variety of cancers.Material/Methods: In this research, we used multiple online bioinformatics websites including ONCOMINE, TCGA, CGGA, TIMER, cBioPortal, GeneMANIA and DAVID to study the expression profiles, prognostic values and immune infiltration correlations of EGFR family in glioma.Results: We found that EGFR and ERBB2 mRNA expression levels were the higher in glioblastoma (GBM, WHO IV) than other grades (WHO grade II&III), While ERBB3 and ERBB4 mRNA expression levels were opposite. EGFR and ERBB2 were notably downregulated in IDH mutant gliomas, while ERBB3 and ERBB4 were the opposite. Besides, ERBB2 and ERBB4 in glioma patients were associated with poor prognosis. In addition, correlation analysis between EGFR family expression and immune infiltrating levels in glioma showed that EGFR family expression and immune infiltrating levels were significantly correlated. PPI network of EGFR family in glioma and enrichment analysis showed that EGFR family and their interactors mainly participated in regulation of cell motility involved integrin receptors and Rho family GTPases.Conclusions: In summary, this study indicates that EGFR family may become potential targets and new prognostic markers for glioma.

show abstract

Dual Targeting of ERBB2/ERBB3 for the Treatment of SLC3A2-NRG1–Mediated Lung Cancer

Cited by 31 publications

References 24 publications

Detection of NRG1 Gene Fusions in Solid Tumors

Detection of NRG1 Gene Fusions in Solid Tumors

Emerging oncogenic fusions other than ALK, ROS1, RET, and NTRK in NSCLC and the role of fusions as resistance mechanisms to targeted therapy

The Expression and Prognostic Values of Epidermal Growth Factor Receptor Family in Glioma

Contact Info

Product

Resources

About