Insulin-like growth factor-1 receptor-targeted therapy for non-small cell lung cancer: a mini review

Abstract

Lung cancer leads all other cancers in both incidence and mortality. Recent advances in underlying molecular pathogenesis have validated a panel of protein tyrosine kinases as new targets in lung cancer treatment. Insulin-like growth factor-1 receptor (IGF-1R) is an important tyrosine kinase receptor involved in cell proliferation, differentiation, metabolism, apoptosis, and angiogenesis. Aberrant activation of IGF-1R is frequently found in patients with lung cancer and contributes to malignant transformation and poor prognosis for patients with lung cancer. In this review, we focused on recent progress in the research of IGF-1R's role in lung cancer development and progression, including its structure and biological function, potential mechanisms of aberrant activation, and related oncogenic effects. We also discussed effective IGF-1R antagonists that are currently registered for clinic trials or are undergoing preclinical study with special emphasis on their antibodies and small molecule tyrosine kinase inhibitors.

Keywords: Insulin-like growth factor; lung cancer; receptor; targeted therapy.

Figure 1

IGF-1R activation and regulation. IGF ligand, IGF-1, or IGF-2 activates IGF-1R and its downstream signaling as modified from the picture in reference [1]. It also causes ligand binding-induced receptor internalization, which degrades IGF-1R through lysosome (normal cells) or proteosome (lung cancer cells) pathways. Sp1 is the major transcriptional factor of the IGF-1R gene and is negatively regulated by p53, BRCA1, and WT1. IGF-1R mAb or IGF-1R TKI blocks IGF-1R activation and inhibits tumor growth.