Although the prognosis of patients with localized prostate cancer is good after surgery, with a favorable response to androgen deprivation therapy, about one third of them invariably relapse, and progress to castration-resistant prostate cancer. Overall, prostate cancer therapies remain scarcely effective, thus it is mandatory to devise alternative treatments enhancing the efficacy of surgical castration and hormone administration. Dysregulation of the phosphoinositide 3-kinase pathway has attracted growing attention in prostate cancer due to the highly frequent association of epigenetic and post-translational modifications as well as to genetic alterations of both phosphoinositide 3-kinase and PTEN to onset and/or progression of this malignancy, and to resistance to canonical androgen-deprivation therapy. Here we provide a summary of the biological functions of the major players of this cascade and their deregulation in prostate cancer, summarizing the results of preclinical and clinical studies with PI3K signaling inhibitors and the reasons of failure independent from genomic changes.

中文翻译：

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PTEN / PI3K / AKT / mTOR信号在前列腺癌中的表达失控：仍然是潜在的可药物治疗靶标吗？

尽管局限性前列腺癌患者的手术后预后良好，对雄激素剥夺治疗的反应良好，但其中约三分之一总是复发，并发展为去势抵抗性前列腺癌。总体而言，前列腺癌疗法仍然几乎无效，因此必须设计出替代疗法以提高手术去势和激素给药的疗效。磷酸肌醇3-激酶途径的失调在前列腺癌中引起了越来越多的关注，这是由于表观遗传学和翻译后修饰的频繁关联以及磷酸肌醇3-激酶和PTEN的遗传改变使其开始和/或发展。恶性肿瘤，以及对常规雄激素剥夺疗法的抵抗力。