GRPR Expression in Metastatic Cancers: A Review of Potential Application of GRPR-Radioligand Therapy.

IF 5.9 2区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Aurélien Callaud, Heying Duan, Elif Hindié, Clément Morgat, Andrei Iagaru
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Abstract

Gastrin-Releasing Peptide Receptor (GRPR) represents a promising molecular target for radionuclide therapy (TRT) across a variety of malignancies due to its overexpression in several tumor types, including prostate, breast, lung, melanoma, cervix, neuroblastoma, head and neck, and colon cancers. While expression patterns vary-with high GRPR expression notably observed in cervix and neuroblastoma cancers-tumor heterogeneity and metastatic profiles remain challenges for patient selection and therapy optimization. Recent advances in GRPR-targeted radiopharmaceutical development have focused on overcoming peptide instability and enhancing tumor uptake, exemplified by novel compounds such as AMTG with improved proteolytic resistance and albumin binding domains to extend circulatory half-life. Furthermore, innovative radionuclides like terbium-161, lead-212, copper-67, cobalt-58 m, and arsenic-77 offer enhanced therapeutic potential beyond the current standard of lutetium-177 through favorable decay characteristics including Auger electron emission and alpha-particle therapy. Preclinical and early clinical studies demonstrate encouraging tumor targeting and therapeutic efficacy with manageable toxicity profiles, particularly in prostate and cervix cancers. However, further investigation into GRPR expression heterogeneity, metastatic distribution, and safety is necessary to refine patient stratification and maximize clinical benefit. This evolving landscape positions GRPR-TRT as a versatile and potent approach, with the potential to expand targeted radionuclide therapy to a broader range of malignancies and improve outcomes in advanced cancers with limited treatment options.

GRPR在转移性癌症中的表达:GRPR放射配体治疗的潜在应用综述。
胃泌素释放肽受体(GRPR)在多种肿瘤中过表达,包括前列腺癌、乳腺癌、肺癌、黑色素瘤、宫颈癌、神经母细胞瘤、头颈癌和结肠癌,是放射性核素治疗(TRT)的一个有希望的分子靶点。虽然表达模式各不相同——在子宫颈和神经母细胞瘤中观察到GRPR的高表达——但肿瘤的异质性和转移特征仍然是患者选择和治疗优化的挑战。grpr靶向放射性药物开发的最新进展集中在克服肽不稳定性和增强肿瘤摄取上,例如AMTG等新型化合物具有改善的蛋白水解抗性和白蛋白结合域,以延长循环半衰期。此外,创新的放射性核素,如铽-161、铅-212、铜-67、钴-58 m和砷-77,通过包括俄热电子发射和α粒子治疗在内的良好衰变特性,提供了比目前标准的镥-177更高的治疗潜力。临床前和早期临床研究证明了令人鼓舞的肿瘤靶向性和治疗效果以及可控的毒性,特别是在前列腺癌和宫颈癌中。然而,进一步研究GRPR的表达异质性、转移分布和安全性对于完善患者分层和最大化临床获益是必要的。这种不断发展的前景使GRPR-TRT成为一种多功能和有效的方法,有可能将靶向放射性核素治疗扩大到更广泛的恶性肿瘤,并改善治疗选择有限的晚期癌症的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Seminars in nuclear medicine
Seminars in nuclear medicine 医学-核医学
CiteScore
9.80
自引率
6.10%
发文量
86
审稿时长
14 days
期刊介绍: Seminars in Nuclear Medicine is the leading review journal in nuclear medicine. Each issue brings you expert reviews and commentary on a single topic as selected by the Editors. The journal contains extensive coverage of the field of nuclear medicine, including PET, SPECT, and other molecular imaging studies, and related imaging studies. Full-color illustrations are used throughout to highlight important findings. Seminars is included in PubMed/Medline, Thomson/ISI, and other major scientific indexes.
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