Prostate Cancer Theranostics Targeting Gastrin-Releasing Peptide Receptors

Baratto, Lucia; Jadvar, Hossein; Iagaru, Andrei

doi:10.1007/s11307-017-1151-1

Cited by 68 publications

(63 citation statements)

References 70 publications

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“…Actively www.nature.com/scientificreports/ targeting tumors with cancer-specific molecules containing fluorescent groups plays an important role in the diagnosis and treatment of OSCC. In recent years, GRPR has been used as a target for cancer diagnosis and treatment of prostate cancer, breast cancer and small cell lung cancer [30][31][32] . Few studies were conducted to investigate the GRPR targeting potential in human head and neck squamous cell carcinoma OSCC.…”

Section: Discussionmentioning

confidence: 99%

Gastrin releasing peptide receptor targeted nano-graphene oxide for near-infrared fluorescence imaging of oral squamous cell carcinoma

Gao

Wang

et al. 2020

Sci Rep

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Oral squamous cell carcinoma (OSCC) is the most common malignant tumor that occurs in the oral mucosa. Pathological biopsy is still the current gold standard for OSCC diagnosis; however, some drawbacks need to be overcome. Therefore, it is urgently needed to find a non-invasive targeted technology for OSCC early diagnosis. Fluorescent optical imaging using near infrared (NIR) dyes tagged to tumor specific target will benefit such developments. Gastrin releasing peptide receptor (GRPR) is an attractive target for OSCC imaging and therapy. In this study, we synthesized nanographene oxide (NGO) nanoparticles with GRPR-specific peptides AF750-6Ahx-Sta-BBN via hydrogen bond and π-π bonds (NGO-BBN-AF750), and investigated their receptor binding, cell uptake and internalization in HSC-3 cells. NGO-BBN-AF750 and AF750-6Ahx-Sta-BBN showed a similar binding affinity to GRPR on HSC-3 cells. In contrast to AF750-6Ahx-Sta-BBN antagonist peptide, NGO-BBN-AF750 showed cellular internalization property. Overall, this study proposes a NGO nanoclustersbased nanoprobe for GRPR targeted near-infrared fluorescence imaging for OSCC. Nanoparticle-based delivery systems have shown highly significant potential in the delivery of a wide range of therapeutic agents. Oral squamous cell carcinoma (OSCC) is the most common malignant tumor that occurs in the head and neck 1. Despite many advanced therapies, the 5-year survival rate of OSCC patients still stagnate at 40-50%. Because of lack of effective diagnostic approaches, over 60% of patients present stages III and IV at the time of diagnosis 2. The histopathological examination of suspected oral mucosa biopsy tissues is considered a gold standard for validation of OSCC 3. However, it has limitations such as laborious, causing pain and time-consuming. In addition, patients with any form of suspected lesion may need to undergo a second biopsy for further confirmation. Therefore, developing sensitive screening methods that are non-invasive and economic, would be necessary to enhance early diagnosis of OSCC and improve the patients' survival. And, effective screening aids to differentiate benign from malignant lesions as well as to avoid complications associated with false diagnosis of oral cancer. Recently, it is proven that optical imaging systems are effective for cancer imaging in hollow organs or as intraoperative imaging tools 4,5. Gastrin-releasing peptide receptor (GRPR) is an attractive target for OSCC imaging and therapy. GRPR, a G protein-coupled receptor, has been proven with high expressions on many human tumors, such as prostate cancer, gastrointestinal stromal, breast cancer, ovarian cancer and small cell lung cancer 6-12. Recently, Lango MN 13 found that GRPR is overexpressed in both head and neck squamous cell carcinoma (HNSCC) tumors and adjacent normal mucosa from HNSCC patients compared with levels in control mucosa from individuals without cancer. Other

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Section: Discussionmentioning

confidence: 99%

Gastrin releasing peptide receptor targeted nano-graphene oxide for near-infrared fluorescence imaging of oral squamous cell carcinoma

Gao

Wang

et al. 2020

Sci Rep

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“…Rivera et al [55] showed that high expression of GRPR alone or both GRP and GRPR, are associated with delayed recurrence (14.1-17 months respectively, p = 0.005) and increased survival (10.1-13.1 months respectively, p = 0.0124), as well as fewer lymph node metastases, making it an attractive prognostic marker [55]. Bombesin analagues (which bind to GRPR) have been used in radiolabelled form for imaging diagnosis, staging, recurrence detection and assessment of mestastasis in prostate cancer patients but have yet to be explored in CRC [56].…”

Section: Pro-gastrin (Pg)/gastrin (G)/gastrin-releasing Peptide (Grp)mentioning

confidence: 99%

The prognostic and therapeutic role of hormones in colorectal cancer: a review

et al. 2018

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Colorectal cancer (CRC) is one of the commonest cancers in Western society with a poor prognosis in patients with advanced disease. Targeted therapy is of increasing interest and already, targeted hormone treatment for breast and prostate cancer has improved survival. The aim of this literature review is to summarise the role of hormones in CRC prognosis and treatment. A literature review of all human and animal in vivo and in vitro studies in the last 20 years, which assessed the role of hormones in CRC treatment or prognosis, was carried out. The hormones described in this review have been subdivided according to their secretion origin. Most of the studies are based on in vitro or animal models. The main findings point to adipokines, insulin and the insulin growth factor axis as key players in the link between obesity, type 2 diabetes mellitus and a subset of CRC. Gut-derived hormones, especially uroguanylin and guanylin are being increasingly investigated as therapeutic targets, with promising results. Using hormones as prognostic and therapeutic markers in CRC is still in the preliminary stages for only a fraction of the hormones affecting the GIT. In light of the increasing interest in tailoring treatment strategies, hormones are an important area of focus in the future of CRC management.

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“…Most GRPR-targeted agents use the C-terminal fragment of the bombesin peptide because of its ability to target the receptor with nanomolar affinity (2,3). Examination of the structure-activity profile of this fragment has revealed numerous highly GRPR-binding derivatives with different pharmacologic profiles in terms of agonistic versus antagonistic character (4)(5)(6). Exceptional work by Maecke's group and others has identified antagonistic analogs (e.g., RM26) that have substantially higher tumor uptake and better nontarget clearance profiles than agonistic analogs (7)(8)(9).…”

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confidence: 99%

Development of Improved Tumor-Residualizing, GRPR-Targeted Agents: Preclinical Comparison of an Endolysosomal Trapping Approach in Agonistic and Antagonistic Constructs

et al. 2019

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Receptor-targeted radiopharmaceuticals based on low-molecularweight carriers offer many clinically advantageous attributes relative to macromolecules but have generally been hampered by their rapid clearance from tumors, thus diminishing tumor-to-nontarget tissue ratios. Herein, we present a strategy using irreversible inhibitors (E-64 derivative) of cysteine cathepsins (CCs) as trapping agents to increase the tumor retention of receptor-targeted agents. Methods: We incorporated these CC-trapping agents into agonistic and antagonistic pharmacophores targeting the gastrin-releasing peptide receptor (GRPR). The synthesized radioconjugates with either an incorporated CC inhibitor or a matching control were examined using in vitro and in vivo models of the GRPR-positive, PC-3 human prostate cancer cell line. Results: From the in vitro studies, multiple techniques confirmed that the CC-trapping, GRPR-targeted constructs were able to increase cellular retention by forming intracellular macromolecule adducts. In PC-3 tumor-bearing xenograft mice, the CC-trapping, GRPR-targeted agonistic and antagonistic constructs led to an approximately 2-fold increase in tumor retention with a corresponding improvement in most tumor-to-nontarget tissue ratios over 72 h. Conclusion: CC endolysosomal trapping provides a pathway to increase the efficacy and clinical potential of low-molecularweight, receptor-targeted agents.

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Prostate Cancer Theranostics Targeting Gastrin-Releasing Peptide Receptors

Cited by 68 publications

References 70 publications

Gastrin releasing peptide receptor targeted nano-graphene oxide for near-infrared fluorescence imaging of oral squamous cell carcinoma

Gastrin releasing peptide receptor targeted nano-graphene oxide for near-infrared fluorescence imaging of oral squamous cell carcinoma

The prognostic and therapeutic role of hormones in colorectal cancer: a review

Development of Improved Tumor-Residualizing, GRPR-Targeted Agents: Preclinical Comparison of an Endolysosomal Trapping Approach in Agonistic and Antagonistic Constructs

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