目前,前列腺癌仍然是男性中发病率第二高的癌症,在欧洲。晚期转移性疾病的治疗效果,特别是转移性去势抵抗性前列腺癌是有限的。前列腺特异性膜抗原(PSMA)是前列腺癌的一个有前途的治疗靶点,看到前列腺癌细胞的大量过度表达。PSMA靶向放射性核素治疗的临床研究显示出良好的临床疗效。然而,观察到的不良反应中,唾液腺功能减退和口干症是最突出的。唾液腺毒性是目前PSMA靶向放射性核素治疗的剂量限制性副作用,更具体地用于PSMA靶向α治疗。迄今为止,唾液腺摄取PSMA靶向化合物的潜在机制以及随后对唾液腺的损伤仍在很大程度上未知。此外,需要针对唾液腺摄取的预防策略或针对唾液腺毒性的治疗策略。这篇综述的重点是关于唾液腺中PSMA靶向化合物的摄取机制的最新知识,以及为研究预防或治疗唾液腺毒性的不同策略而进行的研究。
At present, prostate cancer remains the second most occurring cancer in men, in Europe. Treatment efficacy for therapy of advanced metastatic disease, and metastatic castration-resistant prostate cancer in particular is limited. Prostate-specific membrane antigen (PSMA) is a promising therapeutic target in prostate cancer, seeing the high amount of overexpression on prostate cancer cells. Clinical investigation of PSMA-targeted radionuclide therapy has shown good clinical efficacy. However, adverse effects are observed of which salivary gland hypofunction and xerostomia are among the most prominent. Salivary gland toxicity is currently the dose-limiting side effect for PSMA-targeted radionuclide therapy, and more specifically for PSMA-targeted alpha therapy. To date, mechanisms underlying the salivary gland uptake of PSMA-targeting compounds and the subsequent damage to the salivary glands remain largely unknown. Furthermore, preventive strategies for salivary gland uptake or strategies for treatment of salivary gland toxicity are needed. This
review focuses on the current knowledge on uptake mechanisms of PSMA-targeting compounds in the salivary glands and the research performed to investigate different strategies to prevent or treat salivary gland toxicity.