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
刚刚
共享精神应助猪猪hero采纳,获得10
刚刚
1秒前
1秒前
Sunrise发布了新的文献求助10
2秒前
PSL完成签到,获得积分10
2秒前
2秒前
3秒前
4秒前
liuyf完成签到 ,获得积分10
4秒前
6秒前
6秒前
YJ888发布了新的文献求助10
6秒前
今后应助Lu采纳,获得10
6秒前
EED发布了新的文献求助10
6秒前
88C真是太神奇啦完成签到,获得积分10
7秒前
7秒前
Rondab应助shuyi采纳,获得30
8秒前
酷酷飞烟发布了新的文献求助10
9秒前
10秒前
在水一方应助故意的靳采纳,获得50
11秒前
13秒前
忧郁的鱿鱼完成签到,获得积分10
13秒前
JamesPei应助lm采纳,获得10
15秒前
xww完成签到,获得积分10
15秒前
隐形曼青应助忐忑的阑香采纳,获得10
16秒前
秋半梦发布了新的文献求助10
17秒前
slp完成签到,获得积分20
24秒前
秋半梦完成签到,获得积分10
27秒前
bububusbu完成签到,获得积分10
27秒前
量子星尘发布了新的文献求助10
28秒前
我是老大应助TTm采纳,获得20
29秒前
科研通AI5应助Bressanone采纳,获得10
29秒前
坡坡大王发布了新的文献求助10
30秒前
华仔应助anna采纳,获得10
34秒前
carlin完成签到,获得积分10
36秒前
白子双完成签到,获得积分10
40秒前
FXQ123_范完成签到,获得积分10
40秒前
传奇3应助ran123456采纳,获得30
41秒前
keyan_baby完成签到,获得积分20
42秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 3989115
求助须知:如何正确求助?哪些是违规求助? 3531367
关于积分的说明 11253688
捐赠科研通 3269986
什么是DOI,文献DOI怎么找? 1804868
邀请新用户注册赠送积分活动 882078
科研通“疑难数据库(出版商)”最低求助积分说明 809105