Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms.
The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development and tissue homeostasis. Notably, comprehensive genetic studies in Drosophila and mice in the past decades have demonstrated the crucial role of Wnt signaling in intestinal stem cell maintenance by regulating proliferation, differentiation, and cell-fate decisions. Wnt signaling has also been implicated in a variety of cancers and other diseases. Loss of the Wnt pathway negative regulator adenomatous polyposis coli (APC) is the hallmark of human colorectal cancers (CRC). Recent advances in high-throughput sequencing further reveal many novel recurrent Wnt pathway mutations in addition to the well-characterized APC and β-catenin mutations in CRC. Despite attractive strategies to develop drugs for Wnt signaling, major hurdles in therapeutic intervention of the pathway persist. Here we discuss the Wnt-activating mechanisms in CRC and review the current advances and challenges in drug discovery.
The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
Laura
L
Novellasdemunt
The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom.
Pedro
P
Antas
The Francis Crick Institute, Mill Hill Laboratory, London, United Kingdom Vivian.Li@crick.ac.uk.
Vivian S W
VS
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D060449:Wnt Signaling Pathway / Q000502:physiology*
D000970:Antineoplastic Agents
Wnt signaling pathway; adenomatous polyposis coli; colorectal cancer; drug targeting; small molecules; β-catenin