利用DNA修复缺陷对前列腺癌进行个性化放射药物治疗。

IF 2.3 3区医学 Q3 ONCOLOGY

Urologic Oncology-seminars and Original Investigations Pub Date : 2025-07-28 DOI:10.1016/j.urolonc.2025.07.001

Panagiotis J. Vlachostergios M.D., Ph.D.

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引用次数: 0

摘要

针对前列腺特异性膜抗原（PSMA）的放射性药物治疗已经改变了转移性前列腺癌的治疗方式，但治疗反应的患者间差异仍然是一个关键挑战。新出现的证据表明，DNA修复途径中的缺陷，包括同源重组缺陷（HRD）和错配修复缺陷（MMRd），通过损害损伤解决使肿瘤细胞对电离辐射敏感。正在进行的研究探索整合DNA修复缺陷的基因组图谱的潜力，以优化患者选择和个性化放射性药物策略，如177Lu-PSMA和α -发射偶联物。将靶向辐射与合成致死方法相结合的临床努力正在进行中。针对单个肿瘤DNA修复谱定制放射药物治疗为改善晚期前列腺癌的预后和扩大治疗窗口提供了一个有希望的范例。

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Leveraging DNA repair deficiency to personalize radiopharmaceutical therapy in prostate cancer

Radiopharmaceutical therapies targeting prostate-specific membrane antigen (PSMA) have transformed the management of metastatic prostate cancer, yet inter-patient variability in therapeutic response remains a critical challenge. Emerging evidence indicates that defects in DNA repair pathways, including homologous recombination deficiency (HRD) and mismatch repair deficiency (MMRd), sensitize tumor cells to ionizing radiation by impairing damage resolution. Ongoing research explores the potential of integrating genomic profiling of DNA repair defects to optimize patient selection and personalize radiopharmaceutical strategies such as 177Lu-PSMA and alpha-emitting conjugates. Clinical efforts to combine targeted radiation with synthetic lethality approaches are ongoing. Tailoring radiopharmaceutical therapy to individual tumor DNA repair profiles offers a promising paradigm to improve outcomes and expand therapeutic windows in advanced prostate cancer.

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来源期刊

Urologic Oncology-seminars and Original Investigations 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.70%

发文量

297

审稿时长

7.6 weeks

期刊介绍： Urologic Oncology: Seminars and Original Investigations is the official journal of the Society of Urologic Oncology. The journal publishes practical, timely, and relevant clinical and basic science research articles which address any aspect of urologic oncology. Each issue comprises original research, news and topics, survey articles providing short commentaries on other important articles in the urologic oncology literature, and reviews including an in-depth Seminar examining a specific clinical dilemma. The journal periodically publishes supplement issues devoted to areas of current interest to the urologic oncology community. Articles published are of interest to researchers and the clinicians involved in the practice of urologic oncology including urologists, oncologists, and radiologists.