Prostate-Specific Membrane Antigen: Gateway to Management of Advanced Prostate Cancer.

IF 15.1 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Annual review of medicine Pub Date : 2024-01-29 DOI:10.1146/annurev-med-081522-031439

Lena M Unterrainer, Jeremie Calais, Neil H Bander

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引用次数: 0

Abstract

Prostate-specific membrane antigen (PSMA) as a transmembrane protein is overexpressed by prostate cancer (PC) cells and is accessible for binding antibodies or low-molecular-weight radioligands due to its extracellular portion. Successful targeting of PSMA began with the development of humanized J591 antibody. Due to their faster clearance compared to antibodies, small-molecule radioligands for targeted imaging and therapy of PC have been favored in recent development efforts. PSMA positron emission tomography (PET) imaging has higher diagnostic performance than conventional imaging for initial staging of high-risk PC and biochemical recurrence detection/localization. However, it remains to be demonstrated how to integrate PSMA PET imaging for therapy response assessment and as an outcome endpoint measure in clinical trials. With the recent approval of ¹⁷⁷Lu-PSMA-617 by the US Food and Drug Administration for metastatic castration-resistant PC progressing after chemotherapy, the high value of PSMA-targeted therapy was confirmed. Compared to standard of care, PSMA-based radioligand therapy led to a better outcome and a higher quality of life. This review, focusing on the advanced PC setting, provides an overview of different approved and nonapproved PSMA-targeted imaging and therapeutic modalities and discusses the future of PSMA-targeted theranostics, also with an outlook on non-radiopharmaceutical-based PSMA-targeted therapies.

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前列腺特异性膜抗原：前列腺特异性膜抗原：晚期前列腺癌的治疗之门。

前列腺特异性膜抗原（PSMA）是一种跨膜蛋白，在前列腺癌（PC）细胞中过度表达，由于其细胞外部分可与抗体或低分子量放射性配体结合。PSMA 的成功靶向始于人源化 J591 抗体的开发。与抗体相比，小分子放射性配体的清除速度更快，因此近年来用于 PC 靶向成像和治疗的小分子放射性配体备受青睐。在对高危 PC 进行初步分期和生化复发检测/定位方面，PSMA 正电子发射断层扫描（PET）成像比传统成像具有更高的诊断性能。然而，如何将 PSMA 正电子发射断层成像整合到治疗反应评估中，并作为临床试验的结局终点指标，仍有待论证。最近，美国食品和药物管理局批准了177Lu-PSMA-617用于化疗后进展的转移性阉割耐药PC，证实了PSMA靶向治疗的高价值。与标准疗法相比，基于PSMA的放射性配体疗法能带来更好的疗效和更高的生活质量。本综述以晚期 PC 病例为重点，概述了各种已批准和未批准的 PSMA 靶向成像和治疗模式，并讨论了 PSMA 靶向治疗学的未来，同时还展望了非放射性药物 PSMA 靶向疗法。

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

Annual review of medicine 医学-医学：内科

CiteScore

24.90

自引率

0.00%

发文量

期刊介绍： The Annual Review of Medicine, which has been published since 1950, focuses on important advancements in diverse areas of medicine. These include AIDS/HIV, cardiology, clinical pharmacology, dermatology, endocrinology/metabolism, gastroenterology, genetics, immunology, infectious disease, neurology, oncology/hematology, pediatrics, psychiatry, pulmonology, reproductive medicine, and surgery. The journal's current volume has transitioned from a gated access model to an open access model through the Annual Reviews' Subscribe to Open program. All articles published in the journal are now available under a CC BY license.