Interaction between epidermal growth factor receptor and interleukin‐6 receptor in NSCLC progression

Abstract

Even though the interaction between epithelial growth factor receptor (EGFR) and interleukin-6 receptor (IL-6R) has been found in many tumors, there is a lack of relevant in-depth study of lung cancer. The following study investigates the interaction of EGFR and IL-6R in lung cancer. In the current study, EGFR, IL-6, and glycoprotein 130 (GP130) were highly expressed in non-small cell lung cancer (NSCLC) tissue samples and were associated with clinicopathological features and poor prognosis of patients with NSCLC. Furthermore, the effect of EGF and IL-6 on biological behavior of lung cancer cells (cell proliferation, invasion, cycle, and apoptosis) and the expression of EGFR, GP130, p-protein kinase B (p-AKT), and p-p44/42 mitogen-activated protein kinase (p-p44/42 MAPK) was significantly stronger compared with other treatment groups (all P < 0.05). These results suggest that EGFR and IL-6R have synergistic effects on NSCLC progression. This could help to solve the problem of EGFR inhibitors in the treatment of lung cancer resistance and improve the efficacy of current treatment for lung cancer through a combination of EGFR and IL-6R signaling pathways.

Low expression of IL6R predicts poor prognosis for lung adenocarcinoma

“…At present, a large number of studies have confirmed that IL6R is related to tumors (15)(16)(17)(18). Studies have even shown that IL6 could be used as a prognostic biomarker for cholangiocarcinoma, and IL6R could be used as a therapeutic target for cholangiocarcinoma (38).…”

“…Another study found that IL6R (rs4845626 and rs4329505) polymorphisms were associated with a reduced risk of lung cancer among smokers and nonsmokers (14), and the interaction between epithelial growth factor receptor (EGFR) and IL6R in multiple tumors has been discovered. EGFR mutations and overexpression are known to contribute to the development of lung cancer, with the signaling pathways of EGFR and IL6R having a synergistic role in the occurrence and development of this disease (15). Studies have shown that the expression of IL6 is also closely related to the development of other cancers.…”

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design

“…Curcumin's effects on the tumour microenvironment also include activation of the immune system and suppression of angiogenesis and chemoresistance and immune resistance. Akt, protein kinase B; Bcl-2, B cell lymphoma 2; CAF, cancer-associated fibroblast; COX-2, cyclooxygenase-2; EGF, endothelial growth factor; [128,196,[242][243][244][245]248,249,276,[279][280][281][282][283][284]. NSCLC is associated with dysregulation of numerous signalling and regulatory pathways.…”

“…Figure 4. Simplified model of the effects of curcumin on NSCLC cells[128,196,[242][243][244][245]248,249,276,[279][280][281][282][283][284]. NSCLC…”

Understanding the Complexity of the Tumor Microenvironment in K-ras Mutant Lung Cancer: Finding an Alternative Path to Prevention and Treatment

“…Paradoxically, some models show evidence of accelerated tumorigenesis in early stages of IL-6 depletion (70, 71). However, therapeutic antibodies against IL-6R have decreased tumorigenesis and increased apoptosis in numerous human cancer cell lines synergistically with other targeted therapies such as EGFR inhibitors (71,72). A clinical trial (NCT03337698) using tocilizumab (anti-IL-6R) is underway in patients with metastatic disease who have or have not received previous therapy with conventional chemotherapy plus anti-PD-1/PD-L1 therapy (73).…”