Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment

ABSTRACT

Introduction: Despite remarkable advances in tumor treatment, many patients still die from common tumors (breast, prostate, lung, CNS, colon, and pancreas), and thus, new approaches are needed. Many of these tumors synthesize bombesin (Bn)-related peptides and over-express their receptors (BnRs), hence functioning as autocrine-growth-factors. Recent studies support the conclusion that Bn-peptides/BnRs are well-positioned for numerous novel antitumor treatments, including interrupting autocrine-growth and the use of over-expressed receptors for imaging and targeting cytotoxic-compounds, either by direct-coupling or combined with nanoparticle-technology.

Areas covered: The unique ability of common neoplasms to synthesize, secrete, and show a growth/proliferative/differentiating response due to BnR over-expression, is reviewed, both in general and with regard to the most frequently investigated neoplasms (breast, prostate, lung, and CNS). Particular attention is paid to advances in the recent years. Also considered are the possible therapeutic approaches to the growth/differentiation effect of Bn-peptides, as well as the therapeutic implication of the frequent BnR over-expression for tumor-imaging and/or targeted-delivery.

Expert opinion: Given that Bn-related-peptides/BnRs are so frequently ectopically-expressed by common tumors, which are often malignant and become refractory to conventional treatments, therapeutic interventions using novel approaches to Bn-peptides and receptors are being explored. Of particular interest is the potential of reproducing with BnRs in common tumors the recent success of utilizing overexpression of somatostatin-receptors by neuroendocrine-tumors to provide the most sensitive imaging methods and targeted delivery of cytotoxic-compounds.

KEYWORDS:

• Bombesin
• cancer
• targeted therapy
• nanoparticles
• gastrin-releasing peptide
• prostate cancer
• breast cancer
• lung cancer
• CNS tumor

Article highlights

• Bn-related peptides are frequently ectopically synthesized and secreted by numerous common tumors.

• The BnRs (NMBR [BB1], GRPR [BB2], BRS-3 [BB3]) are one of the receptor classes most frequently ectopically expressed or overexpressed by many common neoplasms (breast, prostate, CNS tumors, lung, pancreas, colon).

• The presence of both ectopically expressed receptors and synthesis of Bn ligands results in autocrine-growth/proliferative/differentiating effects on many of these tumors whose disruption can lead to therapeutic effects.

• Numerous recent studies in vitro, preclinical studies using tumor xenografts and increasingly in human disease, report the use of various approaches to use the overexpression of BnRs to image the primary tumor, tumor extent and recurrences and, show promise. These are reviewed in depth for the common tumors listed above overexpressing BnRs.

• Similarly, the overexpression of BnRs in these tumors, particularly breast and prostate, are being used to target novel cytotoxic agents to the tumors and show promise. Progress in this area is also reviewed and summarized.

This box summarizes the key points contained in the article.

Declaration of interest

This study was supported by intramural funds of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Cancer Institute (NCI), National Institutes of Health (NIH). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.