Nimotuzumab, an EGFR‑targeted antibody, promotes radiosensitivity of recurrent esophageal squamous cell carcinoma

Abstract

Local tumor recurrence is one of the main causes for the failure of esophageal cancer treatment following radiotherapy. Previous studies have demonstrated that epidermal growth factor receptor (EGFR)-targeted therapy combined with radiotherapy is expected to become an effective means to control tumor recurrence. The aim of the present study was to investigate the effect and mechanism of nimotuzumab (an EGFR-targeted antibody) in the treatment of recurrent esophageal carcinoma. The radiation responses of two esophageal squamous carcinoma cell lines, EC109 and TE-1, with or without nimotuzumab, were first evaluated by CCK-8 assay. Colony formation and apoptosis were used to measure anti-proliferation effects. It was demonstrated that nimotuzumab arrested the cell cycle at the G2 phase in vitro. Western blotting and immunofluorescence analysis were used to determine signaling pathway changes. It was observed that nimotuzumab inhibited phosphorylation of EGFR in EC109 cells. Furthermore, recurrent tumor models were established and it was identified that the degree of tumor hypoxia was positively associated with EGFR overexpression. In EC109 cell xenografts, nimotuzumab combined with radiation led to a significant delay in recurrent tumor growth compared with that of radiation alone (P<0.001 for 0 Gy pre-irradiation, P=0.005 for 20 Gy pre-irradiation, P=0.005 for 10 Gy pre-irradiation). These results suggest that nimotuzumab combined with radiation may be an effective means to control recurrent esophageal squamous cell carcinoma with EGFR overexpression.

A novel immune-related radioresistant lncRNAs signature based model for risk stratification and prognosis prediction in esophageal squamous cell carcinoma

“…Therefore, it is particularly important to search for radioresistance-related molecular markers and new radiosensitizers to enhance radio-sensitivity in ESCC cells and improve the survival of ESCC patients with radioresistance. Radioresistance is the focus and difficulty in cancer radiobiology research, which is also a clinically urgent issue ( Wang et al, 2019 ; Yu et al, 2020 ; Sun et al, 2021 ; Liu et al, 2022 ). Genes are an intrinsic determinant of tumor radioresistance, and studies have shown that multiple genes can affect the radioresistance of esophageal cancer ( Huang et al, 2019 ; Wang et al, 2019 ; Hua et al, 2020 ; Yu et al, 2020 ; Han et al, 2021 ; Sun et al, 2021 ; Liu et al, 2022 ).…”

“…Radioresistance is the focus and difficulty in cancer radiobiology research, which is also a clinically urgent issue ( Wang et al, 2019 ; Yu et al, 2020 ; Sun et al, 2021 ; Liu et al, 2022 ). Genes are an intrinsic determinant of tumor radioresistance, and studies have shown that multiple genes can affect the radioresistance of esophageal cancer ( Huang et al, 2019 ; Wang et al, 2019 ; Hua et al, 2020 ; Yu et al, 2020 ; Han et al, 2021 ; Sun et al, 2021 ; Liu et al, 2022 ). Practice has shown that it is common in clinical practice that even patients with esophageal cancer of the same stage and the same pathological type have great differences in the effect of radiotherapy after receiving the same radiotherapy regimen.…”

Establishment of a Novel Risk Score System of Immune Genes Associated With Prognosis in Esophageal Carcinoma

“…The overexpression of epidermal growth factor receptor (EGFR) in ESCC often indicates a poor prognosis (32). It was reported that an ESCC-targeted antibody could improve the radiosensitivity of recurrent ESCC with overexpression of EGFR, suggesting an effective treatment (33). In their in vitro and in vivo model study, Hoi and his team found that chemotherapy upregulated the expression of PD-L1 in ESCC by activating the E G F R / E R K p a t h w a y , s u g g e s t i n g t h a t a n t i -P D -L 1 immunotherapy combined with conventional chemotherapy could achieve a better therapeutic effect (5).…”

Effectiveness and Safety of Targeted Agents Combined With Chemoradiotherapy for the Treatment of Esophageal Cancer: A Network Meta-Analysis

“…Nimotuzumab shows obvious advantages in ORR and epCR and shows a relative advantage in OS results, but PFS results are lacking. Mechanistically, repeated radiotherapy on EC could cause acquired radioresistance and tumor recurrence, and nimotuzumab could inhibit key tumor survival-related protein, DNA repair, and EGFR signaling pathways, thus reversing acquired radiation resistance and increasing sensitivity (42)(43)(44). A retrospective study showed that nimotuzumab combined with CRT can markedly increase the disease control rate and PFS and has a tendency to prolong OS compared to cetuximab combined with CRT for the treatment of locally advanced squamous cell carcinoma (45).…”