医学
PI3K/AKT/mTOR通路
前列腺癌
耐受性
临床试验
肿瘤科
不利影响
雄激素剥夺疗法
癌症
蛋白激酶B
内科学
信号转导
生物
生物化学
作者
Jason Cham,Aparajit Ram Venkateswaran,Munveer S. Bhangoo
标识
DOI:10.1016/j.clgc.2021.07.014
摘要
Prostate cancer is one of leading causes of cancer death among men worldwide. Androgen deprivation therapy is a central part of the prostate cancer treatment algorithm, however, resistance to androgen deprivation commonly leads to disease progression. Mutations in the phosphoinositide-3-kinase pathway (PI3K) have been implicated in cancer progression and the development of castration-resistance. Thus, inhibitors of this pathway and its downstream signaling partners have been studied as potential therapeutic agents to treat metastatic castration resistant prostate cancer (mCRPC). In this article, we review recent clinical results for novel targeted therapies against the PI3K-AKT-mTOR pathway.Trials included in this systemic review were identified through conference abstracts, citations in review articles, PubMed, and ClinicalTrials.gov. Trial eligibility was independent of clinical setting or sample size.A total of 13 prospective clinical trials between 2012 and 2020 were reviewed: Two trials for pan-PI3K inhibitors, 2 trials for selective PI3K inhibitors, 4 trials for AKT inhibitors, 5 trials for mTOR inhibitors, and 1 for a combined PI3K and mTOR inhibitor. All studies were phase I or II studies with primary outcomes of either safety and tolerability or efficacy.Overall, pan-PI3K inhibitors and selective-PI3K inhibitors have not demonstrated clinical efficacy and may have significant adverse effects. AKT inhibitors may have significant adverse effects, but showed some evidence of improved survival. mTORC1 inhibitors show modest efficacy and significant adverse effects.
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