Insulin‐like growth factor‐1 receptor inhibitor, AMG‐479, in cetuximab‐refractory head and neck squamous cell carcinoma

Abstract

Background Recurrent head and neck squamous cell carcinoma (HNSCC) remains a difficult cancer to treat. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents, cetuximab, and AMG-479 (monoclonal antibody against insulin-like growth factor-1 receptor [IGF-1R]). Methods The clinical information was collected by a retrospective medical record review under an Institutional Review Board–approved protocol. From 4 tumors and 2 normal mucosal epithelia, global gene expression, and IGF-1R and dihydrofolate reductase (DHFR) protein levels were determined. Results Effective target inhibition in the tumor was confirmed by the decreased protein levels of total and phospho-IGF-1R after treatment with AMG-479. Decreased level of DHFR and conversion of a gene expression profile associated with cetuximab-resistance to cetuximab-sensitivity were also observed. Conclusion This suggests that the combination of AMG- 479 and MTX or cetuximab may be a promising therapeutic approach in refractory HNSCC.

Heterogeneity in signaling pathways of gastroenteropancreatic neuroendocrine tumors: a critical look at notch signaling pathway

“…5,17 Our results suggest several therapeutic targets including NOTCH1, IGFR1, and cathepsin B. 18,19 Our study also suggests that the expression of certain targets, such as PDGFRB and androgen receptor, may not be worth pursuing.…”

Impact of targeting insulin-like growth factor signaling in head and neck cancers

“…Ganitumab is a fully humanized anti-IGF-1-R monoclonal antibody that interferes with the binding of IGF-1 and IGF-2 and does not cross react with the insulin receptor (IR) that has received a great deal of attention recently. The anticancer properties of ganitumab have been studied in a variety of advanced human solid tumors, including HNSCC, alone and in combination with myriad monoclonal antibodies and chemotherapeutics (43–47). Initial in vitro data were very promising and demonstrated the necessary specificity for IGF-1/2, and efficacy in tumor cell cultures, to warrant in vivo studies and eventually clinical trials.…”

Molecular Basis of Modern Targeted Therapy for Squamous Cell Carcinoma of the Tongue and Oral Mucosa With Monoclonal Antibodies

“…В ходе серии исследований показано, что для предот-вращения активации тирозинкиназы MET необходимы по крайней мере три антитела, действующие на разные эпитопы HGF [54]. В настоящее время доступны два анти-тела против HGF: AV299 (AVEO) и AMG102 (Amgen) [55].…”