Journal ArticleDOI
WNT signalling pathways as therapeutic targets in cancer
Jamie N. Anastas,Randall T. Moon +1 more
TLDR
This work has shown that WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis, and improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can alter WNT signalling in preclinical models.Abstract:
Since the initial discovery of the oncogenic activity of WNT1 in mouse mammary glands, our appreciation for the complex roles for WNT signalling pathways in cancer has increased dramatically. WNTs and their downstream effectors regulate various processes that are important for cancer progression, including tumour initiation, tumour growth, cell senescence, cell death, differentiation and metastasis. Although WNT signalling pathways have been difficult to target, improved drug-discovery platforms and new technologies have facilitated the discovery of agents that can alter WNT signalling in preclinical models, thus setting the stage for clinical trials in humans.read more
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Control of Wnt Receptor Turnover by R-spondin-ZNRF3/RNF43 Signaling Module and Its Dysregulation in Cancer.
TL;DR: The biology of the R-spondin-ZNRF3/RNF43 signaling module, cancer-associated alterations of this signaling module and their value as biomarkers to identify Wnt-addicted tumors are discussed.
Journal ArticleDOI
Glycogen synthase kinase 3 inhibitors induce the canonical WNT/β-catenin pathway to suppress growth and self-renewal in embryonal rhabdomyosarcoma.
Eleanor Y. Chen,Michael DeRan,Myron S. Ignatius,Kathryn Brooke Grandinetti,Ryan Clagg,Karin M. McCarthy,Riadh Lobbardi,Jillian Brockmann,Charles Keller,Xu Wu,David M. Langenau +10 more
TL;DR: An unconventional tumor suppressive role for the canonical WNT/β-catenin pathway in regulating self-renewal of ERMS is identified and therapeutic strategies to target differentiation of TPCs in ERMS are revealed.
Journal Article
Pancreatic cancer stem cells
Ya-Yun Zhu,Zhou Yuan +1 more
TL;DR: This review tries to articulate the complicated signaling pathways regulating the retention of the characteristics of pancreatic cancer stem cells, and seeks to offer insights into the CSCs-relevant targeted therapeutics which are, in the meantime, confronted with bigger challenges than ever.
Journal ArticleDOI
Targeting the WNT Signaling Pathway in Cancer Therapeutics
David Tai,Keith Wells,John J. Arcaroli,Chad M. Vanderbilt,Dara L. Aisner,Wells A. Messersmith,Christopher H. Lieu +6 more
TL;DR: The evidence supporting the WNT pathway in cancer, the therapeutic strategies in modulating this pathway, and potential challenges in drug development are evaluated.
Journal ArticleDOI
Genomics of response to immune checkpoint therapies for cancer: implications for precision medicine.
Jake Conway,Jake Conway,Eric Kofman,Eric Kofman,Shirley S. Mo,Shirley S. Mo,Haitham Elmarakeby,Haitham Elmarakeby,Haitham Elmarakeby,Eliezer M. Van Allen,Eliezer M. Van Allen +10 more
TL;DR: The various biological pathways and emerging biomarkers implicated in response to PD-(L)1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) therapies, including oncogenic signaling pathways, human leukocyte antigen (HLA) variability, mutation and neoantigen burden, microbiome composition, endogenous retroviruses (ERV), and deficiencies in chromatin remodeling and DNA damage repair (DDR) machinery are reviewed.
References
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TL;DR: Integrative analyses suggest new markers for aggressive colorectal carcinoma and an important role for MYC-directed transcriptional activation and repression.
Journal ArticleDOI
Lessons from Hereditary Colorectal Cancer
TL;DR: The authors are grateful to the members of their laboratories for their contributions to the reviewed studies and to F. Giardiello and S. Hamilton for photographs of colorectal lesions.
Journal ArticleDOI
Activation of β-Catenin-Tcf Signaling in Colon Cancer by Mutations in β-Catenin or APC
Patrice J. Morin,Andrew B. Sparks,Vladimir Korinek,Nick Barker,Hans Clevers,Bert Vogelstein,Kenneth W. Kinzler +6 more
TL;DR: Results indicate that regulation of β-catenin is critical to APC's tumor suppressive effect and that this regulation can be circumvented by mutations in either APC or β- catenin.
Journal ArticleDOI
Complex networks orchestrate epithelial–mesenchymal transitions
TL;DR: Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.
Journal ArticleDOI
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC−/− Colon Carcinoma
Vladimir Korinek,Nick Barker,Patrice J. Morin,Dick F. van Wichen,Roel A. de Weger,Kenneth W. Kinzler,Bert Vogelstein,Hans Clevers +7 more
TL;DR: Constitutive transcription of Tcf target genes, caused by loss of APC function, may be a crucial event in the early transformation of colonic epithelium.