Wnt pathway inhibition via the targeting of Frizzled receptors results in decreased growth and tumorigenicity of human tumors

被引：513

作者：

Gurney, Austin ^{[1
]}

Axelrod, Fumiko ^{[1
]}

Bond, Christopher J. ^{[1
]}

Cain, Jennifer ^{[1
]}

Chartier, Cecile ^{[1
]}

Donigan, Lucas ^{[1
]}

Fischer, Marcus ^{[1
]}

Chaudhari, Aurelie ^{[1
]}

Ji, May ^{[1
]}

Kapoun, Ann M. ^{[1
]}

Lam, Andrew ^{[1
]}

Lazetic, Sasha ^{[1
]}

Ma, Shirley ^{[1
]}

Mitra, Satyajit ^{[1
]}

Park, In-Kyung ^{[1
]}

Pickell, Kellie ^{[1
]}

Sato, Aaron ^{[1
]}

Satyal, Sanjeev ^{[1
]}

Stroud, Michelle ^{[1
]}

Hoang Tran ^{[1
]}

Yen, Wan-Ching ^{[1
]}

Lewicki, John ^{[1
]}

Hoey, Timothy ^{[1
]}

机构：

[1] OncoMed Pharmaceut, Redwood City, CA 94063 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 29期

关键词：

differentiation; cancer stem cell; pancreatic; breast; lung; CANCER STEM-CELLS; HUMAN LUNG-CANCER; BETA-CATENIN; COLORECTAL-CANCER; BREAST-CANCER; SELF-RENEWAL; SUPPRESSOR; GENE; ASSOCIATION; EXPRESSION;

D O I：

10.1073/pnas.1120068109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The Wnt/beta-catenin pathway, which signals through the Frizzled (Fzd) receptor family and several coreceptors, has long been implicated in cancer. Here we demonstrate a therapeutic approach to targeting the Wnt pathway with a monoclonal antibody, OMP-18R5. This antibody, initially identified by binding to Frizzled 7, interacts with five Fzd receptors through a conserved epitope within the extracellular domain and blocks canonical Wnt signaling induced by multiple Wnt family members. In xenograft studies with minimally passaged human tumors, this antibody inhibits the growth of a range of tumor types, reduces tumor-initiating cell frequency, and exhibits synergistic activity with standard-of-care chemotherapeutic agents.

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收藏

页码：11717 / 11722

页数：6

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