scholarly journals The Role of EREG/EGFR Pathway in Tumor Progression

2021 ◽  
Vol 22 (23) ◽  
pp. 12828
Author(s):  
Wan-Li Cheng ◽  
Po-Hao Feng ◽  
Kang-Yun Lee ◽  
Kuan-Yuan Chen ◽  
Wei-Lun Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Genetic Mutation ◽  
Alternative Activation ◽  
Driver Mutations ◽  
Viral Oncogene ◽  
Egfr Tki ◽  
Viral Oncogene Homolog

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.

Difference in incidence and pattern of salvage treatment after failure to first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy and standard cytotoxic chemotherapy in pts with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations: Okayama Lung Cancer Study Group experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7576-7576
Author(s):  
Yuka Kato ◽  
Eiki Ichihara ◽  
Katsuyuki Hotta ◽  
Akiko Hisamoto ◽  
Nagio Takigawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Cytotoxic Chemotherapy ◽  
Egfr Mutations ◽  
Deterioration Rate ◽  
Lung Cancer Study Group ◽  
Line Setting ◽  
To Receive ◽  
Egfr Tki

7576 Background: EGFR-TKI (E) therapy yielded a better PFS than standard cytotoxic chemotherapy (C) therapy and a comparable OS in untreated pts with EGFR-mt tumors, suggesting each of the treatments is now crucial for such subpopulation. But, it has not been fully evaluated yet which of each should be initiated first, and to what degree both of two are actually administered in early line setting in the treatment course. We here investigated a potential difference in incidence and pattern of delivery of subsequent crossover therapy after failure to each of the treatments in pts with EGFR-mt tumors. Methods: Consecutive 79 pts with advanced EGFR-mt NSCLC were retrospectively assessed who underwent E therapy (n = 39) or standard C therapy (n = 40) in the 1st-line setting between 2007 and 2011. Results: In E group 16 (41%) of 39 pts were still on 1st-line E therapy. Nine (39%) of the remaining 23 could not receive standard C therapy after failure to E therapy due to symptomatic CNS metastasis(mets) in 6, skeletal events in 2, and patient refusal in 1, whilst in C group only one (3%) of 40 failed to receive subsequent E therapy because of relapse (carcinomatous lymphangitis) (χ2-test; p < .001). Also, at the time of relapse to the 1-st line therapy, PS deteriorated more frequently in E group (8/23 vs. 7/40; p = .042) and, relapse with symptomatic CNS mets seemed frequently observed in E group (6/23 vs. 4/40; p = .093). Multivariate analysis revealed type of regimens undergone in the 1st-line setting (E vs. C) correlated with failure of administration of subsequent crossover therapy (odd ratio: 3.224, 95%CI: .1.032 – 5,417, p = .004). Conclusions: It seems that pts with EGFR-mt tumors who were treated with 1st-line C had better opportunity to receive post-progression E therapy than those treated with 1st-line E had chance to receive subsequent C therapy, possibly due to difference in PS deterioration rate and relapse pattern.

scholarly journals Evaluation of Patients with Lung Cancer Treated with Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor

2018 ◽  
Vol 04 (02) ◽  
pp. 048-053
Author(s):  
Laksmi Wulandari ◽  
Anna Febriani ◽  
Farah Fatmawati ◽  
Gatot Soegiarto
Keyword(s):  
Lung Cancer ◽  
General Hospital ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
First Line ◽  
Epidermal Growth ◽  
Egfr Mutated ◽  
Egfr Tki

AbstractEpidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI) is currently the standard therapy for EGFR-mutated non–small cell lung cancer (NSCLC). Gefitinib is the first EGFR-TKI marketed in Indonesia and has been used since 2012 in Dr. Soetomo General Hospital, a tertiary hospital in Surabaya, East Java, Indonesia. Although the drug had shown some positive results, the overall treatment outcome for Indonesian patients has not been reported yet. The aim of the study is to evaluate the progression-free survival (PFS), overall survival (OS), and subjective response of gefitinib as first-line treatment in advanced EGFR-mutated NSCLC patients in Dr. Soetomo General Hospital. This retrospective study includes all eligible patients treated from 2013 to 2016. Demographic data, performance status, tumor histopathologic types, treatment response, and adverse effects (AEs) during the treatment course were collected from patient's medical records. Objective response was based on RECIST 1.1. Quality of life was assessed using Eq. 5D questionnaire. From evaluable data of 63 patients, median PFS was 8.3 months (95% confidence interval [CI: 6.50–10.2) with median OS of 16 months (95% CI: 11.9–20.2). Eq. 5D scores were decreased in 21 (33.3%) patients, stable in 22 (34.9%), and increased in 20 (31.7%). The most common side effects were itchy skin rash in 52 (82%) patients and diarrhea in 29 (46%). Gefitinib as first-line therapy provides a good objective response and is generally well tolerated in patients with EGFR-mutated NSCLC in Dr. Soetomo General Hospital.

Sign in / Sign up

Export Citation Format

Share Document