Radioimmunotherapy of solid tumors targeting a cell-surface protein, FZD10: therapeutic efficacy largely depends on radiosensitivity

Hanaoka, Hirofumi; Katagiri, Toyomasa; Fukukawa, Chikako; Yoshioka, Hiroki; Yamamoto, Shinji; Iida, Yasuhiko; Higuchi, Tetsuya; Oriuchi, Noboru; Paudyal, Bishnuhari; Paudyal, Pramila; Nakamura, Yusuke; Endo, Keigo

doi:10.1007/s12149-009-0265-1

Cited by 18 publications

(20 citation statements)

References 19 publications

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“…FZD6 upregulation in colorectal cancer, neuroblastoma and triple-negative breast cancer is involved in stem-like features, EMT and drug resistance (193–196). Based on FZD5 upregulation in solid tumors, including RNF43 -mutated pancreatic cancer (197,198), FZD7 upregulation in breast cancer, colorectal cancer, glioma and hepatocellular carcinoma (199–203) and FZD10 upregulation in breast cancer, colorectal cancer and synovial sarcoma (204–207), anti-FZD5 IgG, anti-FZD7 mAb and anti-FZD10 mAbs have been developed for cancer therapy. Vantictumab (OMP-18R5), initially isolated as an FZD7-binding antibody, is a broad-spectrum anti-FZD mAb that reacts with FZD1, FZD2, FZD5, FZD7 and FZD8 (208), which all belong to the FZD1/2/7 or FZD5/8 subfamily among the FZD family (204).…”

Section: Therapeutics Targeting Wnt Signaling Cascadesmentioning

confidence: 99%

Molecular genetics and targeted therapy of WNT-related human diseases (Review)

Katoh¹,

2017

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Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription. Germline mutations in WNT signaling molecules cause hereditary colorectal cancer, bone diseases, exudative vitreoretinopathy, intellectual disability syndrome and PCP-related diseases. APC or CTNNB1 mutations in colorectal, endometrial and prostate cancers activate the WNT/β-catenin signaling cascade. RNF43, ZNRF3, RSPO2 or RSPO3 alterations in breast, colorectal, gastric, pancreatic and other cancers activate the WNT/β-catenin, WNT/STOP and other WNT signaling cascades. ROR1 upregulation in B-cell leukemia and solid tumors and ROR2 upregulation in melanoma induce invasion, metastasis and therapeutic resistance through Rho-ROCK, Rac-JNK, PI3K-AKT and YAP signaling activation. WNT signaling in cancer, stromal and immune cells dynamically orchestrate immune evasion and antitumor immunity in a cell context-dependent manner. Porcupine (PORCN), RSPO3, WNT2B, FZD5, FZD10, ROR1, tankyrase and β-catenin are targets of anti-WNT signaling therapy, and ETC-159, LGK974, OMP-18R5 (vantictumab), OMP-54F28 (ipafricept), OMP-131R10 (rosmantuzumab), PRI-724 and UC-961 (cirmtuzumab) are in clinical trials for cancer patients. Different classes of anti-WNT signaling therapeutics are necessary for the treatment of APC/CTNNB1-, RNF43/ZNRF3/RSPO2/RSPO3- and ROR1-types of human cancers. By contrast, Dickkopf-related protein 1 (DKK1), SOST and glycogen synthase kinase 3β (GSK3β) are targets of pro-WNT signaling therapy, and anti-DKK1 (BHQ880 and DKN-01) and anti-SOST (blosozumab, BPS804 and romosozumab) monoclonal antibodies are being tested in clinical trials for cancer patients and osteoporotic post-menopausal women. WNT-targeting therapeutics have also been applied as reagents for in vitro stem-cell processing in the field of regenerative medicine.

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Section: Therapeutics Targeting Wnt Signaling Cascadesmentioning

confidence: 99%

Molecular genetics and targeted therapy of WNT-related human diseases (Review)

Katoh¹,

2017

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“…For example, various forms of cancer shown to over express Wnt1 demonstrated decreased size and survival when treated with a Wnt1-blocking antibody [42,43]. Similarly, sarcomas that over express the FZD10 receptor have shown significant regression in response to FZD10 antibodies bound to the radioisotope Yttrium-90 [44]. Other strategies being used to target a broader range of Wnts in malignancies that display marked alteration in numerous Wnt ligands include the use of a decoy FZD receptor to bind Wnts before they can trigger Wnt signaling in cells.…”

Section: Use Of Biological Therapiesmentioning

confidence: 99%

Targeting the Wnt signaling pathways in pulmonary arterial hypertension

Perez

Yuan

Alastalo

et al. 2014

Drug Discovery Today

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Pulmonary arterial hypertension (PAH) is a life-threatening disorder that is associated with elevated pulmonary pressures and right heart failure resulting from progressive loss and thickening of small pulmonary arteries. Despite their ability to improve symptoms, current therapies fail to prevent disease progression, leaving lung transplantation as the only therapy in end-stage PAH. To overcome the limitations of current therapies, there is an active search for disease-modifying agents capable of altering the natural history of, and improving clinical outcomes in, PAH. The Wnt signaling pathways have emerged as attractive treatment targets in PAH given their role in the preservation of pulmonary vascular homeostasis and the recent development of Wnt-specific compounds and biological therapies capable of modulating pathway activity. In this review, we summarize the literature describing the role of Wnt signaling in the pulmonary circulation and discuss promising advances in the field of Wnt therapeutics that could lead to novel clinical therapies capable of preventing and/or reversing pulmonary vascular pathology in patients with this devastating disease.

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“…As a therapeutic approach, some groups have used anti-human FZD10 antibody for cancer treatment. For instance, mouse anti-human FZD10 monoclonal antibody labeled with Yttrium-90 ( 90 Y) decreased in vivo tumor growth in mice with FZD10-positive synovial sarcoma cell lines SYO-1 and FZD10-transfected colon cancer cell line DLD-1 (109, 154). …”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Frizzled homolog proteins, microRNAs and Wnt signaling in cancer

Ueno

Hirata

Hinoda

et al. 2012

Intl Journal of Cancer

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Wnt signaling pathways play important roles in tumorigenesis and are initiated by binding of Wnt to various receptors including frizzleds (FZDs). FZDs are one of several families of receptors comprised of FZD/LRP/ROR2/RYK in the Wnt signaling pathway. Expression of some FZD receptors are up-regulated, thereby activating the Wnt signaling pathway and is correlated with cancer malignancy and patient outcomes (recurrence and survival) in many cancers. The FZD family contains ten genes in humans and their function has not been completely examined including the regulatory mechanisms of FZD genes in cancer. Knockdown of FZDs may suppress the Wnt signaling pathway resulting in decreased cell growth, invasion, motility and metastasis of cancer cells. Recently a number of microRNAs (miRNAs) have been identified and reported to be important in several cancers. MiRNAs regulate target gene expression at both the transcription and translation levels. The study of miRNA is a newly emerging field and promises to be helpful in understanding the pathogenesis of FZDs in cancer. Also miRNAs may be useful in regulating FZDs in cancer cells. Therefore the aim of this review is to discuss current knowledge of the functional mechanisms of FZDs in cancer, including regulation by miRNAs and the potential for possible use of miRNAs and FZDs in future clinical applications.

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Radioimmunotherapy of solid tumors targeting a cell-surface protein, FZD10: therapeutic efficacy largely depends on radiosensitivity

Abstract: The therapeutic efficacy of RIT seems to largely depend on the tumor radiosensitivity.

Cited by 18 publications

References 19 publications

Molecular genetics and targeted therapy of WNT-related human diseases (Review)

Molecular genetics and targeted therapy of WNT-related human diseases (Review)

Targeting the Wnt signaling pathways in pulmonary arterial hypertension

Frizzled homolog proteins, microRNAs and Wnt signaling in cancer

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