Targeted therapy in advanced metastatic colorectal cancer: Current concepts and perspectives

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 withmetastatic 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-ⅠandⅡand 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.

Preclinical therapy of benign prostatic hyperplasia with neuropeptide hormone antagonists

Benign prostatic hyperplasia(BPH)is a pathologic condition of the prostate described as a substantial increase in its number of epithelial and stromal cells.BPH may significantly reduce the quality of life due to the initiation of bladder outlet obstruction and lower urinary tract syndromes.Current medical therapies mostly consist of inhibitors of 5α-reductase orα1-adrenergic blockers;their efficacy is often insufficient.Antagonistic analogs of neuropeptide hormones are novel candidates for the management of BPH.At first,antagonists of luteinizing hormone-releasing hormone(LHRH)have been introduced to the therapy aimed to reduce serum testosterone levels.However,they have also been found to produce an inhibitory activity on local LHRH receptors in the prostate as well as impotence and other related side effects.Since then,several preclinical and clinical studies reported the favorable effects of LHRH antagonists in BPH.In contrast,antagonists of growth hormone-releasing hormone(GHRH)and gastrin-releasing peptide(GRP)have been tested only in preclinical settings and produce significant reduction in prostate size in experimental models of BPH.They act at least in part,by blocking the action of respective ligands produced locally on prostates through their respective receptors in the prostate,and by inhibition of autocrine insulin-like growth factors-Ⅰ/Ⅱand epidermal growth factor production.GHRH and LHRH antagonists were also tested in combination resulting in a cumulative effect that was greater than that of each alone.This article will review the numerous studies that demonstrate the beneficial effects of antagonistic analogs of LHRH,GHRH and GRP in BPH,as well as suggesting a potential role for somatostatin analogs in experimental therapies.