A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors

El–Gamal, Mohammed I.; Mewafi, Nada H.; Abdelmotteleb, Nada E.; Emara, Minnatullah A.; Tarazi, Hamadeh; Sbenati, Rawan M.; Madkour, Moustafa M.; Zaraei, Seyed–Omar; Shahin, Afnan I.; Anbar, Hanan S.

doi:10.3390/molecules26237376

Cited by 37 publications

(33 citation statements)

References 142 publications

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“…Generally, cancer has been linked to mutations in the ERBB4 gene [ 25 ], which in this study was confirmed as a highly unstable gene. No information was found on the sequenced P.Q264* missense mutation in this gene, even if this has been already sequenced in a colon cancer cell line [ 26 ].…”

Section: Discussionsupporting

confidence: 64%

Genomic Landscape Alterations in Primary Tumor and Matched Lymph Node Metastasis in Hormone-Naïve Prostate Cancer Patients

Russo

Bonacci

Bivona

et al. 2022

Cancers

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Background: Prostate cancer (PCa) is a disease with a wide range of clinical manifestations. Up to the present date, the genetic understanding of patients with favorable or unfavorable prognosis is gaining interest for giving the appropriate tailored treatment. We aimed to investigate genetic changes associated with lymph node metastasis in a cohort of hormone-naïve Pca patients. Methods: We retrospectively analyzed data from 470 patients who underwent surgery for PCa between 2010 and 2020 at the Department of Urology, University of Catania. Inclusion criteria were patients with lymph node metastasis and patients with PCa with extra capsular extension (pT3) and negative lymph node metastasis. The final cohort consisted of 17 different patients (11 PCa with lymph node metastasis and 6 PCa without lymph node metastasis). Through the cBioPortal online tool, we analyzed gene alterations and their correlations with clinical factors. Results: A total of 688 intronic, synonym and nonsynonym mutations were sequenced. The gene with the most sequenced mutations was ERBB4 (83 mutations, 12% of 688 total), while the ones with the lower percentage of mutations were AKT1, FGFR2 and MLH1 (1 mutation alone, 0.14%). Conclusion: In the present study we found mostly concordance concerning the ERBB4 mutation between both primary PCa samples and matched lymph node metastasis, underlining that the identification of alterations in the primary tumor is extremely important for cancer prognosis prediction.

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Section: Discussionsupporting

confidence: 64%

Genomic Landscape Alterations in Primary Tumor and Matched Lymph Node Metastasis in Hormone-Naïve Prostate Cancer Patients

Russo

Bonacci

Bivona

et al. 2022

Cancers

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“…The pathway analysis results suggest that MAPK and NOTCH1 are involved in cancer progression at evolving state, followed by enriched PI3K/AKT, ERBB4 and MET pathways at maintaining and adaptive states. This implies that patients stratified by the evolutionary state at the time of diagnosis could benefit from the drugs targeting these pathways, many of which were already approved or being investigated in clinical trials (Bonello et al, 2018; Diaz-Padilla et al, 2015; El-Gamal et al, 2021; Konstantinopoulos et al, 2021; Vergote et al, 2020). Importantly, MAPK, PI3K/AKT and ERBB4 pathways remain unaffected by platinum-taxane chemotherapy and are active also in relapses.…”

Section: Discussionmentioning

confidence: 99%

Evolutionary states and trajectories characterized by distinct pathways stratify ovarian high-grade serous carcinoma patients

Lahtinen

Lavikka

et al. 2022

Preprint

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Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we characterized HGSC evolutionary states using whole-genome sequencing data from 214 samples of 55 HGSC patients in the prospective, longitudinal, multiregion DECIDER study. Comparison of the tissues revealed that site-of-origin samples have 70% more unique clones than the metastatic tumors or ascites. By integrating clonal composition and topology of HGSC tumors we discovered three evolutionary states that represent a continuum from genomically highly variable to stable tumors with significant association to treatment response. The states and their evolutionary trajectories were characterized by unique, targetable pathways, which were validated with RNA-seq data. Our study reveals that genomic heterogeneity is unaffected by the current standard-of-care and pinpoints effective treatment targets for each group. All genomics data are available via an interactive visualization platform for rapid exploration.

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“…DNA-seq in CC-PDX and primary tumors showed several mutations, including those in genes encoding FLT3, ERBB4, CDKN2A, Kinase Insert Domain Receptor (KDR), fibroblast growth factor recep-tor 2 (FGFR2), enhancer of zeste homolog 2 (EZH2), SMAD Family Member 4 (SMAD4), ataxia telangiectasia mu-tated (ATM), SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1 (SMARCB1), Serine/threonine kinase 11 (STK11), and RB1. ERBB4 is a member of the EGFR family, comprising four transmembrane tyrosine kinases [ 43 ]. FGFR2 belongs to the FGFR family [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization

Miyamoto

Tanaka

Hirosuna

et al. 2022

Cancers

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Patient-derived xenograft (PDX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies, and can be developed by the heterotopic or orthotopic grafting of surgically resected tumors into immunodeficient mice. We report the PDX models of cervical cancer and demonstrate the similarities among original and different generations of PDX tumors. Fresh tumor tissues collected from 22 patients with primary cervical cancer were engrafted subcutaneously into NOD.CB17-PrkdcSCID/J mice. Histological and immunohistochemical analyses were performed to compare primary and different generations of PDX tumors. DNA and RNA sequencing were performed to verify the similarity between the genetic profiles of primary and PDX tumors. Total RNA in extracellular vesicles (EVs) released from primary and PDX tumors was also quantified to evaluate gene expression. The total tumor engraftment rate was 50%. Histologically, no major differences were observed between the original and PDX tumors. Most of the gene mutations and expression patterns related to carcinogenesis and infiltration were similar between the primary tumor and xenograft. Most genes associated with carcinogenesis and infiltration showed similar expression levels in the primary tumor and xenograft EVs. Therefore, compared with primary tumors, PDX models could be potentially more useful for translational research.

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A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors

Cited by 37 publications

References 142 publications

Genomic Landscape Alterations in Primary Tumor and Matched Lymph Node Metastasis in Hormone-Naïve Prostate Cancer Patients

Genomic Landscape Alterations in Primary Tumor and Matched Lymph Node Metastasis in Hormone-Naïve Prostate Cancer Patients

Evolutionary states and trajectories characterized by distinct pathways stratify ovarian high-grade serous carcinoma patients

Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization

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