Published online May 28, 2014. doi: 10.3748/wjg.v20.i20.6102
Revised: February 20, 2014
Accepted: March 12, 2014
Published online: May 28, 2014
The introduction of new cytotoxic substances as well as agents that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling has improved clinical outcome of patients with metastatic colorectal cancer (mCRC). In this review we summarize the most relevant clinical data on VEGF and EGFR targeting regimens in mCRC. The effects of available treatment strategies for mCRC are often temporary, with resistance and disease progression developing in most patients. Thus, new treatment strategies are urgently needed. Some GI peptides including gastrin and gastrin releasing peptide, certain growth factors such as insulin-like growth factor-I and II and neuropeptides such as growth hormone releasing hormone (GHRH) are implicated in the growth of CRC. Experimental investigations in CRC with antagonistic analogs of bombesin/gastrin-releasing peptide, GHRH, and with cytotoxic peptides that can be targeted to peptide receptors on tumors, are summarized in the second part of the review.
Core tip: Our review evaluates the most recent clinical data on therapeutic reagents designed to target the vascular endothelial growth factor and epidermal growth factor receptor signaling pathways in colorectal cancer. As colorectal cancers express receptors for bombesin/gastrin-releasing peptide, growth hormone-releasing hormone, somatostatin as well as luteinizing hormone-releasing hormone, we review the implications of these pathways in the growth of colorectal cancers and summarize experimental data and clinical studies performed to date with regard to the antiproliferative action of antagonistic peptide analogs of these receptors as well as their cytotoxic analogs and their status as drug candidates for the treatment of metastatic colorectal cancer.