Insulin-like Growth Factor-1 Receptor (IGF-1R) Kinase Inhibitors in Cancer Therapy: Advances and Perspectives

Abstract

The insulin-like growth factors (IGF) and their receptors play pivotal roles in cellular signaling transduction and thus regulate cell growth, differentiation, apoptosis, transformation and other important physiological progresses. The insulin-like growth factor 1 receptor (IGF-1R) mainly engages in the Ras/mitogen-activated protein kinase (MAPK) pathway and the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, and also forms cross-talk with the epidermal growth factor receptor (EGFR) pathway. Currently, it draws more attention since its overexpression has been demonstrated in various human cancers, such as colorectal cancer, breast cancer, prostate cancer and lung tumors, thus the strategy targeting the IGF-1R would be promising in treatment of these cancers. There are already dozens of agents developed for the inhibition of IGF-1R, which are categorized into monoclonal antibodies, small molecule inhibitors and so on. While in this review, small molecule inhibitors would be the focus for detailed discussion. Herein, we updated previously reported research papers and reviews in this field and summarized developments of small molecule inhibitors up to 2011. Finally, we proposed the application of network pharmacology methods to reconsider the clinical use of inhibitors with concomitant IR inhibition or other kinases inhibition, hoping that more optimal combinations would be obtained for cancer therapy.

Estrogen Receptor Beta-Mediated Proliferative Inhibition and Apoptosis in Human Breast Cancer by Calycosin and Formononetin

“…IGF-1R signaling could control cell growth and participate in the development of normal tissues and malignancy [15,16]. At present, epidemiological studies have correlated increased IGF-1 serum levels with risk of breast cancer, so inhibition of IGF-1R signaling can serve as new target for breast cancer therapy [17,18].…”

MiRNA Synergistic Network Construction and Enrichment Analysis for Common Target Genes in Small-cell Lung Cancer

“…Much evidence indicated that overexpression and activation of MAPK can result in progression of various cancer (Xue et al, 2012). In this study, many genes involved in MAPK pathway were predicted to be regulated synergistically by miRNAs in cilque0.…”

Novel type of plasmin inhibitors: Providing insight into P4 moiety and alternative scaffold to pyrrolopyrimidine

“…Some fused pyrimidines like purines, pteridines and pyrrolopyrimidines, have become an important structural motif in many pharmaceutical agents. 23 Otherwise, a benzimidazole scaffold, being a versatile structural motif, could also be considered a viable starting point in drug discovery. [24][25][26] Pyrrolopyrimidine and benzimidazole have the similar ring system but differ only by the position and number of nitrogens on the aromatic ring.…”