Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7
The Wnt signalling pathway plays a crucial role in tissue homeostasis and cancer biology due to its regulation of cellular processes, including proliferation, migration, and stem cell activity. Frizzled receptor 7 (FZD7) (a member of the F-class G protein-coupled receptors) has emerged as a key Wnt...
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MDPI AG
2025-05-01
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| author | Kieran Hodson Hector M. Arredondo William E. Humphrey Dustin J. Flanagan Elizabeth Vincan Karl Willert Helen B. Pearson Toby J. Phesse |
| author_facet | Kieran Hodson Hector M. Arredondo William E. Humphrey Dustin J. Flanagan Elizabeth Vincan Karl Willert Helen B. Pearson Toby J. Phesse |
| author_sort | Kieran Hodson |
| collection | DOAJ |
| description | The Wnt signalling pathway plays a crucial role in tissue homeostasis and cancer biology due to its regulation of cellular processes, including proliferation, migration, and stem cell activity. Frizzled receptor 7 (FZD7) (a member of the F-class G protein-coupled receptors) has emerged as a key Wnt receptor within this pathway, which is elevated in several human malignancies. FZD7 is notably upregulated in gastrointestinal, breast, pancreatic, and hepatocellular carcinomas and transmits oncogenic Wnt signalling through canonical and non-canonical pathways. FZD7 promotes tumour initiation, and emerging evidence implicates FZD7 in cancer stem cell maintenance and epithelial–mesenchymal transition (EMT), reinforcing its role in metastasis. Therapeutic strategies targeting FZD7 have shown promise, including FZD7-specific monoclonal antibody-drug conjugates (ADCs), human single-chain fragment variable (scFVs) antibodies, and nanoparticles. Notably, our recent development of FZD7-ADC has demonstrated tumour-selective cytotoxicity with reduced off-target effects, positioning FZD7 as an attractive therapeutic target. Additionally, nanoparticle-based drug delivery systems have enhanced the precision of existing chemotherapies by targeting FZD7-expressing tumour cells. Despite significant advances, clinical translation remains a challenge due to potential on-target toxicity and the complexity of tumour microenvironments. Future research should focus on optimising delivery systems, refining antibody specificity, and conducting comprehensive preclinical and clinical trials. This review will focus on novel discoveries regarding FZD7 in cancer and provide an update on our original review on this subject in 2016. Additionally, we present new figures generated by our group using the publicly available Pan-Cancer Atlas RNAseq datasets, highlighting FZD7 expression patterns in patient samples. This integrated approach aims to provide updated insights into the function of FZD7 during cancer and its growing status as an attractive target for therapy. In summary, FZD7 stands out as a promising molecular target in cancer therapy due to its selective overexpression in tumours, functional role in Wnt-driven oncogenesis, and potential for innovative therapeutic applications. This review underscores the critical need for the continued exploration of FZD7-targeted therapies to improve patient outcomes in cancer treatment. |
| format | Article |
| id | doaj-art-98ce7eca8dc84211acecc51698bb9d68 |
| institution | DOAJ |
| issn | 2413-4155 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-98ce7eca8dc84211acecc51698bb9d682025-08-20T03:16:39ZengMDPI AGSci2413-41552025-05-01726110.3390/sci7020061Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7Kieran Hodson0Hector M. Arredondo1William E. Humphrey2Dustin J. Flanagan3Elizabeth Vincan4Karl Willert5Helen B. Pearson6Toby J. Phesse7The European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UKThe European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UKThe European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UKMonash Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, AustraliaDepartment of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, AustraliaSchool of Medicine, University California San Diego, La Jolla, CA 92093, USAThe European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UKThe European Cancer Stem Cell Research Institute, School of Biosciences, Cardiff University, Cardiff CF24 4HQ, UKThe Wnt signalling pathway plays a crucial role in tissue homeostasis and cancer biology due to its regulation of cellular processes, including proliferation, migration, and stem cell activity. Frizzled receptor 7 (FZD7) (a member of the F-class G protein-coupled receptors) has emerged as a key Wnt receptor within this pathway, which is elevated in several human malignancies. FZD7 is notably upregulated in gastrointestinal, breast, pancreatic, and hepatocellular carcinomas and transmits oncogenic Wnt signalling through canonical and non-canonical pathways. FZD7 promotes tumour initiation, and emerging evidence implicates FZD7 in cancer stem cell maintenance and epithelial–mesenchymal transition (EMT), reinforcing its role in metastasis. Therapeutic strategies targeting FZD7 have shown promise, including FZD7-specific monoclonal antibody-drug conjugates (ADCs), human single-chain fragment variable (scFVs) antibodies, and nanoparticles. Notably, our recent development of FZD7-ADC has demonstrated tumour-selective cytotoxicity with reduced off-target effects, positioning FZD7 as an attractive therapeutic target. Additionally, nanoparticle-based drug delivery systems have enhanced the precision of existing chemotherapies by targeting FZD7-expressing tumour cells. Despite significant advances, clinical translation remains a challenge due to potential on-target toxicity and the complexity of tumour microenvironments. Future research should focus on optimising delivery systems, refining antibody specificity, and conducting comprehensive preclinical and clinical trials. This review will focus on novel discoveries regarding FZD7 in cancer and provide an update on our original review on this subject in 2016. Additionally, we present new figures generated by our group using the publicly available Pan-Cancer Atlas RNAseq datasets, highlighting FZD7 expression patterns in patient samples. This integrated approach aims to provide updated insights into the function of FZD7 during cancer and its growing status as an attractive target for therapy. In summary, FZD7 stands out as a promising molecular target in cancer therapy due to its selective overexpression in tumours, functional role in Wnt-driven oncogenesis, and potential for innovative therapeutic applications. This review underscores the critical need for the continued exploration of FZD7-targeted therapies to improve patient outcomes in cancer treatment.https://www.mdpi.com/2413-4155/7/2/61frizzled receptor 7cancertherapyRNAseq |
| spellingShingle | Kieran Hodson Hector M. Arredondo William E. Humphrey Dustin J. Flanagan Elizabeth Vincan Karl Willert Helen B. Pearson Toby J. Phesse Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7 Sci frizzled receptor 7 cancer therapy RNAseq |
| title | Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7 |
| title_full | Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7 |
| title_fullStr | Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7 |
| title_full_unstemmed | Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7 |
| title_short | Targeting Cancer with Paris’ Arrow: An Updated Perspective on Targeting Wnt Receptor Frizzled 7 |
| title_sort | targeting cancer with paris arrow an updated perspective on targeting wnt receptor frizzled 7 |
| topic | frizzled receptor 7 cancer therapy RNAseq |
| url | https://www.mdpi.com/2413-4155/7/2/61 |
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