2023年3月18日 · In this large, real-life pan-cancer patient cohort, our results indicate that PIK3CA/PIK3R1 mutations are widely spread, and plead in favour of evaluating the efficacy of PI3K inhibitors outside...

2024年3月20日 · Pharmacological inhibition of either mTOR or STAT3 significantly improved renal function and reduced apoptosis and inflammation. Interestingly, inhibition of STAT3 with pharmacological inhibitors or small interfering RNA blocked LPS-induced mTOR activation in renal tubular cells, indicating a role of STAT3 in mTOR activation.

2017年6月12日 · Zhang et al. survey the PI3K/AKT/mTOR pathway in >10,000 human cancers across 32 types. In addition to known molecular events, some rare PIK3CA and PIK3R1 mutations activate the pathway, partial copy loss of PTEN or STK11 is associated with poor patient survival, and IDH1 or VHL mutations can confer mTOR activity.

In prostate cancer cell lines, PIK3R1 knockdown resulted in increased cell proliferation and AKT activity, including insulin-stimulated AKT activity. In cell lines and organoids, PIK3R1 loss/mutation was associated with increased sensitivity to AKT inhibitors.

PIK3/Akt/mTor pathway alterations were defined as mutations in Akt1, mTOR, PIK3CA, PIK3CB, PIK3R1, PTEN, TSC1, and TSC2. Endpoints of interests were radiographic progression-free survival (rPFS), time to development of castration resistant prostate cancer …

2023年8月23日 · The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis ...

PI3K通路可以在多个节点上被药理学抑制，包括pan-PI3K和同种型特异性抑制剂，只靶向TORC1或同时靶向TORC1和TORC2的mTOR抑制剂以及AKT抑制剂，这些抑制剂可以直接抑制PI3K活性。 值得注意的是，选择性mTOR抑制剂仅显示有限的长期功效，可能是由于RTK下游TORC1信号传导的反馈抑制的释放，导致PI3K / AKT活化增加。 为了解决这个难题，已经开发了许多双PI3K / mTOR抑制剂。 该图显示在不同临床开发水平下的抑制剂，突出了靶标和组织 …

2015年2月5日 · We genotyped five potentially functional PIK3R1 and mTOR SNPs in 1116 esophageal squamous cell cancer (ESCC) patients and 1117 cancer-free controls to assess their associations with ESCC risk.

2024年2月27日 · Chromatin immunoprecipitation assay also proved the binding of STAT3 to PIK3R1 gene promoter in LPS-treated kidney tubular cells. In addition, knockdown of PIK3R1 suppressed mTOR activation...

2024年3月20日 · These findings highlight the dysregulation of mTOR and STAT3 pathways as critical mechanisms underlying the inflammatory and apoptotic phenotypes observed in renal tubular cells during septic AKI, suggesting the STAT3/ PIK3R1/mTOR pathway as a therapeutic target of septic AKI.