On target? Strategies and progress in the development of therapies for colorectal cancer targeted against WNT signalling.
Chemotherapy is an integral part of treatment for colorectal cancer (CRC), especially in the context of metastatic cancer. Targeted therapies in the form of monoclonal antibodies directed against the endothelial growth factor receptor or the vascular endothelial growth factor have met with success, and have demonstrated the advantages of molecularly targeted therapy in colorectal cancer. Nevertheless, CRC remains a major cause of death, which demonstrates the urgent need for improved treatment strategies. The pathway activated by the Wingless-type mouse mammary tumour virus integration site (WNT) family members is constitutively active and promotes cancer growth in the majority of CRCs. As a result, there has been interest in developing therapeutics that circumvent it either by inhibiting WNT-mediated transcription or by inactivating the target genes. This review considers the current therapies approved for use in CRC and discusses the progress with therapies designed to target the WNT signalling pathway.
McDonald
S L
SL
Colorectal Cancer Genetics, Institute for Cell and Molecular Sciences, Barts and The London School of Medicine and Dentistry, London, UK.
Silver
A R
AR
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; C495270:CTNNB1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin