Genomic aberrations of the PTEN tumour suppressor gene are among the most common in prostate cancer. Inactivation of PTEN by deletion or mutation is identified in ∼20% of primary prostate tumour samples at radical prostatectomy and in as many as 50% of castration-resistant tumours. Loss of phosphatase and tensin homologue (PTEN) function leads to activation of the PI3K–AKT (phosphoinositide 3-kinase–RAC-alpha serine/threonine-protein kinase) pathway and is strongly associated with adverse oncological outcomes, making PTEN a potentially useful genomic marker to distinguish indolent from aggressive disease in patients with clinically localized tumours. At the other end of the disease spectrum, therapeutic compounds targeting nodes in the PI3K–AKT–mTOR (mechanistic target of rapamycin) signalling pathway are being tested in clinical trials for patients with metastatic castration-resistant prostate cancer. Knowledge of PTEN status might be helpful to identify patients who are more likely to benefit from these therapies. To enable the use of PTEN status as a prognostic and predictive biomarker, analytically validated assays have been developed for reliable and reproducible detection of PTEN loss in tumour tissue and in blood liquid biopsies. The use of clinical-grade assays in tumour tissue has shown a robust correlation between loss of PTEN and its protein as well as a strong association between PTEN loss and adverse pathological features and oncological outcomes. In advanced disease, assessing PTEN status in liquid biopsies shows promise in predicting response to targeted therapy. Finally, studies have shown that PTEN might have additional functions that are independent of the PI3K–AKT pathway, including those affecting tumour growth through modulation of the immune response and tumour microenvironment.

PTEN抑癌基因的基因组畸变在前列腺癌中最为常见。通过缺失或突变使PTEN失活在〜在根治性前列腺切除术中有20％的原发性前列腺肿瘤样本以及多达50％的去势抵抗性肿瘤。磷酸酶和张力蛋白同源物（PTEN）功能的丧失会导致PI3K–AKT（磷酸肌醇3激酶–RAC-α丝氨酸/苏氨酸蛋白激酶）通路的激活，并与不良的肿瘤学结局密切相关，从而使PTEN成为可能有用的基因组区分临床上局部肿瘤患者的惰性疾病与侵袭性疾病的标志物。在疾病谱的另一端，针对PI3K–AKT–mTOR（雷帕霉素的机械靶标）信号转导通路中的结节的治疗性化合物正在针对转移性去势抵抗性前列腺癌患者的临床试验中进行测试。了解PTEN状态可能有助于识别更可能从这些疗法中受益的患者。为了能够将PTEN状态用作预后和预测性生物标志物，已经开发了经过分析验证的测定法，用于可靠且可重复地检测肿瘤组织和血液活检中的PTEN丢失。在肿瘤组织中使用临床级别的检测方法已显示出肿瘤的损失之间存在密切的相关性。PTEN及其蛋白，以及PTEN丢失与不良病理特征和肿瘤结局之间有很强的联系。在晚期疾病中，评估液体活检中的PTEN状态显示出预测靶向治疗反应的希望。最后，研究表明，PTEN可能具有独立于PI3K–AKT途径的其他功能，包括那些通过调节免疫应答和肿瘤微环境而影响肿瘤生长的功能。