Presence of mutations in TSC1, TSC2, NF1, NF2 or STK11 genes was assessed using targeted-next generation sequencing (NGS). All eligible patients were treated with everolimus at an initial dose of 10 mg orally once daily in cycles of 28 days. The primary endpoint of this study was overall response rate (ORR).

2025年3月11日 · STK11 activates AMPK under conditions of energetic stress, which in turn activates TSC1/2 4. TSC1/TSC2 represses Rheb, a key activator of mTORC1.

The present results suggest that genetic variants of the STK11, PRKAA1, and TSC1 genes could be used as prognostic biomarkers for patients with surgically resected colorectal cancer.

STK11, also known as LKB1, activates mTOR through activation of AMPK and phosphorylation of TSC2, whereas NF1 prevents the downstream activation of the mTOR pathway by terminating the active state of RAS proteins (4, 5). Mutations in TSC1, TSC2, STK11 and NF1 genes can lead to mTOR pathway dysregulation and promote tumor cell growth (6).

2012年8月16日 · Germline mutations of the Liver Kinase b1 (LKB1/STK11) tumor suppressor gene have been linked to Peutz-Jeghers Syndrome (PJS), an autosomal-dominant, cancer-prone disorder in which patients develop neoplasms in several organs, including the …

Accordingly, based on the assumption that genetic variations in the LKB1-AMPK-mTOR signaling pathway can change the intracellular signal in terms of metabolic reprogramming, the present study analyzed 18 single nucleotide polymorphisms (SNPs) of the STK11, PRKAA1, TSC1/2, and mTOR genes and their impact on the survival of patients with ...

2017年6月12日 · 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.

2010年7月9日 · Serine/threonine protein kinase 11 (STK11) and phosphatase tensin homolog deleted on chromosome 10 (PTEN) link insulin sensitivity and metabolic signaling to inflammation and other hormonal factors and colorectal cancer.

研究发现，HDAC家族中的HDAC3是LKB1突变型NSCLC生长所必需的，先前未被发现的HDAC3靶基因——FGFR1，还介导了此类肿瘤对MEK抑制剂曲美替尼的耐药。 基于上述发现，Reuben等人提出了针对LKB1突变型NSCLC的靶向联合治疗新策略：HDAC3抑制剂entinostat联合MEK抑制剂曲美替尼，二者联合用药在动物实验中有效抑制了NSCLC的肿瘤进展。 论文首页截图. 尽管HDAC3抑制剂作为治疗药物取得了很大的临床进展，但HDAC3在肿瘤发生中的潜在作用在很 …

2024年4月15日 · 本研究首次提出的STK11缺陷转录表型，相比于传统的STK11突变分型更能筛选免疫治疗原发耐药的人群，为推动精准免疫治疗、新药研发提供了新的思路和策略。