ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications

Jin, Wook

doi:10.3390/jcm9072255

Cited by 16 publications

(11 citation statements)

References 155 publications

(166 reference statements)

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“…The expression of the erythroblastic leukemia viral oncogene homolog (ERBB) family is closely linked to tumor progression through the constitutive activation of downstream signaling, such as the epidermal growth factor (EGF) receptor (EGFR) pathway or through a somatic mutation; ERBB expression is enhanced during tumor microenvironment (TME) formation, cancer progression, and drug-resistance [ 1 ]. The ERBB family comprises transmembrane receptor tyrosine kinases, including the ERBB1/ EGFR)/HER (human EGF receptor) 1, ERBB2/HER2/Neu, ERBB3/HER3, and ERBB4/HER4 [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of EREG/EGFR Pathway in Tumor Progression

Cheng

Feng

Lee

et al. 2021

IJMS

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Aberrant activation of the epidermal growth factor receptor (EGFR/ERBB1) by erythroblastic leukemia viral oncogene homolog (ERBB) ligands contributes to various tumor malignancies, including lung cancer and colorectal cancer (CRC). Epiregulin (EREG) is one of the EGFR ligands and is low expressed in most normal tissues. Elevated EREG in various cancers mainly activates EGFR signaling pathways and promotes cancer progression. Notably, a higher EREG expression level in CRC with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) is related to better efficacy of therapeutic treatment. By contrast, the resistance of anti-EGFR therapy in CRC was driven by low EREG expression, aberrant genetic mutation and signal pathway alterations. Additionally, EREG overexpression in non-small cell lung cancer (NSCLC) is anticipated to be a therapeutic target for EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, recent findings indicate that EREG derived from macrophages promotes NSCLC cell resistance to EGFR-TKI treatment. The emerging events of EREG-mediated tumor promotion signals are generated by autocrine and paracrine loops that arise from tumor epithelial cells, fibroblasts, and macrophages in the tumor microenvironment (TME). The TME is a crucial element for the development of various cancer types and drug resistance. The regulation of EREG/EGFR pathways depends on distinct oncogenic driver mutations and cell contexts that allows specific pharmacological targeting alone or combinational treatment for tailored therapy. Novel strategies targeting EREG/EGFR, tumor-associated macrophages, and alternative activation oncoproteins are under development or undergoing clinical trials. In this review, we summarize the clinical outcomes of EREG expression and the interaction of this ligand in the TME. The EREG/EGFR pathway may be a potential target and may be combined with other driver mutation targets to combat specific cancers.

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Section: Introductionmentioning

confidence: 99%

The Role of EREG/EGFR Pathway in Tumor Progression

Cheng

Feng

Lee

et al. 2021

IJMS

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“…GSEA indicated that the differentially expressed genes induced by OLFML3 knockdown were enriched in the ErbB signaling pathway. The ErbB family of receptor tyrosine kinases consists of four closely related members: EGFR, HER2, HER3 and HER4 [ 44 ]. This family plays key roles in tumor growth, metastasis and therapeutic resistance through the activation of downstream pathways, such as the Ras/MAPK and PI3K/AKT pathways [ 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling

et al. 2023

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Although temozolomide (TMZ) provides significant clinical benefit for glioblastoma (GBM), responses are limited by the emergence of acquired resistance. Here, we demonstrate that exosomal circCABIN1 secreted from TMZ-resistant cells was packaged into exosomes and then disseminated TMZ resistance of receipt cells. CircCABIN1 could be cyclized by eukaryotic translation initiation factor 4A3 (EIF4A3) and is highly expressed in GBM tissues and glioma stem cells (GSCs). CircCABIN1 is required for the self-renewal maintenance of GSCs to initiate acquired resistance. Mechanistically, circCABIN1 regulated the expression of olfactomedin-like 3 (OLFML3) by sponging miR-637. Moreover, upregulation of OLFML3 activating the ErbB signaling pathway and ultimately contributing to stemness reprogramming and TMZ resistance. Treatment of GBM orthotopic mice xenografts with engineered exosomes targeting circCABIN1 and OLFML3 provided prominent targetability and had significantly improved antitumor activity of TMZ. In summary, our work proposed a novel mechanism for drug resistance transmission in GBM and provided evidence that engineered exosomes are a promising clinical tool for cancer prevention and therapy. Graphical Abstract

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“…Other inhibitors are currently being examined in different trials, as summarized in a recent review on this issue[ 36 ]. Other genetic aberrations, such as those involving the ERRB family and proto-oncogene tyrosine-protein kinase 1, represent possible targets for CCA therapy; some drugs are under evaluation[ 37 ].…”

Section: Cca Pharmacological Treatment: the Futurementioning

confidence: 99%

Moving forward in the treatment of cholangiocarcinoma

Manzia¹,

Parente²,

Lenci³

et al. 2021

WJGO

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Despite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome.

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ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications

Cited by 16 publications

References 155 publications

The Role of EREG/EGFR Pathway in Tumor Progression

The Role of EREG/EGFR Pathway in Tumor Progression

Exosome-transmitted circCABIN1 promotes temozolomide resistance in glioblastoma via sustaining ErbB downstream signaling

Moving forward in the treatment of cholangiocarcinoma

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