In the last decades, the development of PET/CT radiopharmaceuticals, targeting the Prostate-Specific Membrane Antigen (PSMA), changed the management of prostate cancer (PCa) patients thanks to its higher diagnostic accuracy in comparison with conventional imaging both in staging and in recurrence. Alongside molecular imaging, PSMA was studied as a therapeutic agent targeted with various isotopes. In 2021, results from the VISION trial led to the Food and Drug Administration (FDA) approval of [177Lu]Lu-PSMA-617 as a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) and set the basis for a radical change in the future perspectives of PCa treatment and the history of Nuclear Medicine. Despite these promising results, primary resistance in patients treated with single-agent [177Lu]Lu-PSMA-617 remains a real issue. Emerging trials are investigating the use of [177Lu]Lu-PSMA-617 in combination with other PCa therapies in order to cover the multiple oncologic resistance pathways and to overcome tumor heterogeneity. In this review, our aim is to retrace the history of PSMA-targeted therapy from the first preclinical studies to its future applications in PCa.
近几十年来，靶向前列腺特异性膜抗原（PSMA）的PET/CT放射性药物的研发，因其在分期和复发检测中较传统影像学具有更高的诊断准确性，改变了前列腺癌患者的诊疗模式。除分子影像应用外，PSMA作为治疗靶点与多种放射性核素结合的研究也同步展开。2021年，VISION临床试验的结果促使美国食品药品监督管理局（FDA）批准[¹⁷⁷Lu]Lu-PSMA-617作为转移性去势抵抗性前列腺癌的新型疗法，这为前列腺癌治疗前景和核医学发展史的根本性变革奠定了基础。尽管成果显著，但单药[¹⁷⁷Lu]Lu-PSMA-617治疗中的原发性耐药仍是亟待解决的难题。新兴临床试验正探索将其与其他前列腺癌疗法联用，以期覆盖多重肿瘤耐药通路并克服肿瘤异质性。本文旨在系统回顾PSMA靶向治疗从前沿临床前研究到未来临床应用的发展历程。
肿瘤(癌症)患者之家