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前列腺癌治疗及PSMA诊疗学的现状

The current status of prostate cancer treatment and PSMA theranostics.

作者信息

Uemura Motohide, Watabe Tadashi, Hoshi Seiji, Tanji Ryo, Yaginuma Kei, Kojima Yoshiyuki

机构信息

Department of Urology, Fukushima Medical University School of Medicine, 1, Hikarigaoka, Fukushima 960-1295, Japan.

Department of Urology, Iwase General Hospital, Sukagawa, Fukushima, Japan.

出版信息

Ther Adv Med Oncol. 2023 Jul 3;15:17588359231182293. doi: 10.1177/17588359231182293. eCollection 2023.

Abstract

In the treatment of cancer, understanding the disease status, or accurate staging, is extremely important, and various imaging techniques are used. Computed tomography (CT), magnetic resonance imaging, and scintigrams are commonly used for solid tumors, and advances in these technologies have improved the accuracy of diagnosis. In the clinical practice of prostate cancer, CT and bone scans have been considered especially important for detecting metastases. Nowadays, CT and bone scans are called conventional methods because positron emission tomography (PET), especially prostate-specific membrane antigen (PSMA)/PET, is extremely sensitive in detecting metastases. Advances in functional imaging, such as PET, are advancing the diagnosis of cancer by allowing information to be added to the morphological diagnosis. Furthermore, PSMA is known to be upregulated depending on the malignancy of the prostate cancer grade and resistance to therapy. Therefore, it is often highly expressed in castration-resistant prostate cancer (CRPC) with poor prognosis, and its therapeutic application has been attempted for around two decades. PSMA theranostics refers to a type of cancer treatment that combines both diagnosis and therapy using a PSMA. The theranostic approach uses a radioactive substance attached to a molecule that targets PSMA protein on cancer cells. This molecule is injected into the patient's bloodstream and can be used for both imaging the cancer cells with a PET scan (PSMA PET imaging) and delivering radiation directly to the cancer cells (PSMA-targeted radioligand therapy), with the aim of minimizing damage to healthy tissue. Recently, in an international phase III trial, the impact of Lu-PSMA-617 therapy was studied in patients with advanced PSMA-positive metastatic CRPC who had previously been treated with specific inhibitors and regimens. The trial revealed that Lu-PSMA-617 significantly extended both progression-free survival and overall survival compared to standard care alone. Although there was a higher incidence of grade 3 or above adverse events with Lu-PSMA-617, it did not negatively impact the patients' quality of life. PSMA theranostics is currently being studied and used primarily for the treatment of prostate cancer, but it has the potential to be applied to other types of cancers as well.

摘要

在癌症治疗中,了解疾病状态或准确分期极为重要,为此会使用各种成像技术。计算机断层扫描(CT)、磁共振成像和闪烁扫描常用于实体瘤,这些技术的进步提高了诊断的准确性。在前列腺癌的临床实践中,CT和骨扫描被认为对检测转移灶尤为重要。如今,CT和骨扫描被称为传统方法,因为正电子发射断层扫描(PET),尤其是前列腺特异性膜抗原(PSMA)/PET,在检测转移灶方面极其敏感。PET等功能成像技术的进步通过为形态学诊断增添信息,推动了癌症诊断的发展。此外,已知PSMA会根据前列腺癌分级的恶性程度和对治疗的抗性而上调。因此,它在预后较差的去势抵抗性前列腺癌(CRPC)中通常高度表达,其治疗应用已尝试了约二十年。PSMA诊疗学是指一种使用PSMA将诊断与治疗相结合的癌症治疗方式。这种诊疗方法使用附着在靶向癌细胞上PSMA蛋白的分子上的放射性物质。该分子被注入患者的血液中,可用于通过PET扫描对癌细胞进行成像(PSMA PET成像)以及直接向癌细胞递送辐射(PSMA靶向放射性配体疗法),目的是将对健康组织的损害降至最低。最近,在一项国际III期试验中,研究了Lu-PSMA-617疗法对先前接受过特定抑制剂和治疗方案的晚期PSMA阳性转移性CRPC患者的影响。试验表明,与单纯标准治疗相比,Lu-PSMA-617显著延长了无进展生存期和总生存期。尽管Lu-PSMA-617导致3级及以上不良事件的发生率较高,但并未对患者的生活质量产生负面影响。PSMA诊疗学目前主要用于前列腺癌的治疗研究,但它也有可能应用于其他类型的癌症。

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