Impact of the PI3K-alpha inhibitor alpelisib on everolimus resistance and somatostatin receptor expression in an orthotopic pancreatic NEC xenograft mouse model

依维莫司 医学 神经内分泌肿瘤 安慰剂 内科学 肿瘤科 mTOR抑制剂的发现与发展 药理学 PI3K/AKT/mTOR通路 泌尿科 病理 生物 替代医学 细胞凋亡 生物化学
作者
Ajay-Mohan Mohan,Sonal Prasad,Fabian Schmitz-Peiffer,Catharina Lange,Mathias Lukas,Eva J. Koziolek,Jakob Albrecht,Daniel Messroghli,Ulrike Stein,Matthias Ilmer,Katharina Wang,Laura Schober,Astrid Reul,Julian Maurer,Juliane Friemel,Achim Weber,Richard A. Zuellig,Constanze Hantel,Ralph Fritsch,Martín Reincke,Karel Pacák,Ashley Grossman,Christoph J. Auernhammer,Felix Beuschlein,Winfried Brenner,Nicola Beindorff,Svenja Nölting
出处
期刊:Endocrine-related Cancer [Bioscientifica]
卷期号:31 (1) 被引量:1
标识
DOI:10.1530/erc-23-0041
摘要

The mechanistic target of rapamycin complex 1 (mTORC1) inhibitor everolimus is one of the few approved therapies for locally advanced and metastatic neuroendocrine tumours (NETs). However, after initial disease stabilisation, most patients develop resistance within 1 year. Our aim was to overcome resistance to everolimus by additional treatment with the PI3K-alpha inhibitor alpelisib in an everolimus-resistant orthotopic pancreatic neuroendocrine carcinoma xenograft mouse model. Female SCID mice underwent laparoscopic pancreatic transplantation of everolimus-sensitive (BON1KDMSO) or everolimus-resistant (BON1RR2) NET cells. Both groups were further divided into four treatment groups: placebo, everolimus, alpelisib, and everolimus + alpelisib (combination). Oral treatment was started at a tumour volume of approximately 140 mm3 and continued until 1900-2000 mm3, validated by weekly MRI. Somatostatin receptor expression and tumour viability were analysed by 68Ga-DOTATOC and 18F-FDG PET/CT. Everolimus resistance of the BON1RR2 tumours was confirmed. In the everolimus-sensitive group, everolimus alone, alpelisib alone, and combination treatment significantly prolonged survival, compared to placebo, while in the BON1RR2 group, only combination treatment significantly prolonged survival compared to placebo, but neither everolimus nor alpelisib alone. Placebo-treated everolimus-sensitive tumours grew more rapidly (median survival 45 days), compared to placebo-treated everolimus-resistant tumours (60 days). Within the everolimus-sensitive group, the combination-treated mice showed the longest median survival (52 days). Of all groups, the everolimus-resistant combination-treated group survived longest (69 days). Combination treatment with everolimus and alpelisib seems promising to overcome everolimus resistance in neuroendocrine neoplasms, and should be further examined in a clinical trial.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
旺仔同学发布了新的文献求助10
1秒前
RX信完成签到,获得积分10
2秒前
mumufan完成签到,获得积分10
2秒前
无花果应助晴云采纳,获得10
2秒前
啊标完成签到,获得积分10
2秒前
耕牛热完成签到,获得积分10
2秒前
bsn完成签到 ,获得积分10
3秒前
Akim应助乌拉拉采纳,获得10
4秒前
夏傥完成签到,获得积分10
5秒前
5秒前
彭博完成签到 ,获得积分10
6秒前
SICHEN完成签到,获得积分10
6秒前
韩_完成签到,获得积分10
7秒前
nnnnn完成签到 ,获得积分10
8秒前
鉨汏闫完成签到,获得积分10
8秒前
8秒前
mahliya完成签到,获得积分10
9秒前
耕牛热发布了新的文献求助10
9秒前
天天快乐应助zzz采纳,获得10
10秒前
整齐的白凡完成签到,获得积分10
10秒前
坐雨赏花完成签到 ,获得积分10
10秒前
查理fofo完成签到,获得积分10
12秒前
Shandongdaxiu完成签到 ,获得积分10
14秒前
丘比特应助旺仔同学采纳,获得10
14秒前
科研通AI2S应助旺仔同学采纳,获得10
14秒前
Jasper应助旺仔同学采纳,获得10
14秒前
量子星尘发布了新的文献求助10
14秒前
14秒前
小二郎应助坚强莺采纳,获得10
14秒前
15秒前
火星上的糖豆完成签到,获得积分10
15秒前
时尚战斗机应助sl采纳,获得10
15秒前
16秒前
zz完成签到,获得积分10
16秒前
非凡梦完成签到,获得积分10
16秒前
晴云发布了新的文献求助10
18秒前
dddd完成签到 ,获得积分10
18秒前
LuciusHe完成签到,获得积分10
19秒前
lhj完成签到,获得积分10
19秒前
Leslie完成签到,获得积分10
19秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
Research on Disturbance Rejection Control Algorithm for Aerial Operation Robots 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038426
求助须知:如何正确求助?哪些是违规求助? 3576119
关于积分的说明 11374556
捐赠科研通 3305834
什么是DOI,文献DOI怎么找? 1819339
邀请新用户注册赠送积分活动 892678
科研通“疑难数据库(出版商)”最低求助积分说明 815029