High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients

Abstract

A statistically significant association was observed between high coexpression of both IGFR-1 and EGFR and worse DFS in early NSCLC patients.

Clinical significance of immunohistochemical expression of insulin-like growth factor-1 receptor and matrix metalloproteinase-7 in resected non-small cell lung cancer

“…Cappuzzo et al (18) reported that a positive IGF-1R expression was significantly associated with squamous cell histology and grade III differentiation. Ludovini et al (19) reported that IGF-1R protein overexpression was associated with larger tumor size. Merrick et al (20) showed that higher IGF-1R scores were associated with adenocarcinoma and never-smokers.…”

“…Dziadziuszko et al (17) evaluated 189 NSCLCs and showed that the IGF-1R gene copy number is of prognostic value; nonetheless, IGF-1R protein expression upon immunohistochemical analysis was not related to survival. Ludovini et al (19) reported that IGF-1R protein expression alone was not significantly associated with survival, although high co-expression of both IGF-1R and epidermal growth factor receptor was associated with shorter Table IV. Subset analysis of overall survival in NSCLC.…”

A stable IgG-like bispecific antibody targeting the epidermal growth factor receptor and the type I insulin-like growth factor receptor demonstrates superior anti-tumor activity

“…[14][15][16] The interplay of these two receptor pathways may lead to resistance by the tumor to inhibition of one receptor via compensatory upregulation/activation of the reciprocal receptor, and dual inhibition of EGFR and IGF-1R has been shown to improve anti-tumor activity and overcome resistance to therapy against a single receptor in preclinical models. [17][18][19][20][21][22][23][24] Moreover, co-expression of EGFR and IGF-1R has been reported in many human tumors, including lung, colorectal and pancreatic carcinoma, [25][26][27] supporting dual targeting of these two receptors in these indications. Clinically, EGFR inhibitors are known to be efficacious in only a subpopulation of cancer patients, and intense research for molecular predictors of clinical outcomes to EGFR targeted therapies has identified K-Ras mutation as a predictive biomarker of resistance to EGFR mAbs treatment in colorectal cancer and EGFR gene mutation or high copy number as strong indicators of response to EGFR TKIs in lung cancer.…”

A fibronectin scaffold approach to bispecific inhibitors of epidermal growth factor receptor and insulin-like growth factor-I receptor

“…17,18 Overexpression of EGFR and IGF-IR in NSCLC patients led to shorter disease-free survival. 19 It was also shown that dual silencing of IGF-IR and EGFR decreased proliferation and increased apoptosis in colon carcinoma cells. 20 Additionally, resistance to treatment with the EGFR inhibitor AG1478 increased IGF-IR levels, 21 and resistance to the EGFR inhibitor gefitinib was associated with a heterodimerization of EGFR with IGF-IR.…”