yttrium Y 90 tabituximab barzuxetan (OTSA101-DTPA-90Y) / OncoTherapy - LARVOL DELTA

Phase I Study of Radiolabeled OTSA101-DTPA in Patients With Relapsed or Refractory Synovial Sarcoma (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: OncoTherapy Science, Inc. | N=20 ➔ 12 | Recruiting ➔ Terminated; Some of the raw materials for the investigational drug are difficult to obtain and expensive.

Enrollment change • Trial termination • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Head-to-head comparison of three chelates reveals DOTAGA promising for Ac labeling of anti-FZD10 antibody OTSA101. (PubMed, Cancer Sci) - "The therapeutic and adverse effects were not significantly different between the three conjugates. Our findings indicate that among the three evaluated chelates, DOTAGA appears to be the most promising chelate to produce Ac-labeled OTSA101 with high binding affinity and high radiochemical yields while providing high absorbed doses to tumors and limited absorbed doses to bone marrow."

Head-to-Head • Journal • Hematological Malignancies • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • FZD10

Phase I Study of Radiolabeled OTSA101-DTPA in Patients With Relapsed or Refractory Synovial Sarcoma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: OncoTherapy Science, Inc. | Trial completion date: Dec 2022 ➔ Mar 2024 | Trial primary completion date: Dec 2022 ➔ Mar 2024

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

FZD10-targeted α-radioimmunotherapy with Ac-labeled OTSA101 achieves complete remission in a synovial sarcoma model. (PubMed, Cancer Sci) - "Ac-labeled OTSA101 provided a high BED for tumors and achieved a 60% complete response in the synovial sarcoma mouse model SYO-1. RIT with Ac-labeled OTSA101 is a promising therapeutic option for synovial sarcoma."

Clinical • Journal • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Recent updates on Wnt signaling modulators: a patent review (2014-2020). (PubMed, Expert Opin Ther Pat) - "Lorecivivint, Wnt inhibitor, for the treatment of knee osteoarthritis and SM-04554, Wnt activator, for the treatment of androgenetic alopecia are currently under Phase III. Other molecules like LGK-974, RXC-004, ETC-159, CGX-1321, PRI-724, CWP-232291 and BC-2059 are also under different stages of clinical development for the treatment of cancer. Antibody based Wnt modulator, OTSA101-DTPA-90Y is currently under Phase I for the treatment of relapsed or refractory synovial sarcoma while OMP-18R5 is under Phase I for metastatic breast cancer. Ongoing preclinical and clinical trials will define the role of the Wnt pathway in different therapeutic areas and have opened new opportunities."

Journal • Review • Alopecia • Alzheimer's Disease • Breast Cancer • CNS Disorders • Hepatology • Immunology • Nephrology • Oncology • Osteoarthritis • Pain • Renal Disease • Rheumatology • Sarcoma • Solid Tumor • Synovial Sarcoma

Phase I Study of Radiolabeled OTSA101-DTPA in Patients With Relapsed or Refractory Synovial Sarcoma (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: OncoTherapy Science, Inc.; Trial completion date: May 2021 ➔ Dec 2022; Trial primary completion date: May 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Solid Tumor

Molecular subtypes based on DNA methylation predict prognosis in lung squamous cell carcinoma. (PubMed, BMC Cancer) - "Models based on differences in DNA methylation levels may help to classify the molecular subtypes of LUSC patients, and provide more individualized treatment recommendations and prognostic assessments for different clinical subtypes. GNAS, FZD2, FZD10 are the core three genes that may be related to the prognosis of LUSC patients."

Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • GNAS

Construction and Validation of Predictive Model to Identify Critical Genes Associated with Advanced Kidney Disease. (PubMed, Int J Genomics) - "FZD10 represented the highest score (F score = 21) in predictive model. Our results demonstrated that FZD10, FOXD4, PPP3R1, and UCP2 might be critical genes in CKD progression."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Nrf1 Is Endowed with a Dominant Tumor-Repressing Effect onto the Wnt/β-Catenin-Dependent and Wnt/β-Catenin-Independent Signaling Networks in the Human Liver Cancer. (PubMed, Oxid Med Cell Longev) - "Notably, we identified that β-catenin is not a target gene of Nrf1, but this CNC-bZIP factor contributes to differential or opposing expression of other critical genes, such as CDH1, Wnt5A, Wnt11A, FZD10, LEF1, TCF4, SMAD4, MMP9, PTEN, PI3K, JUN, and p53, each of which depends on the positioning of distinct cis-regulatory sequences (e.g., ARE and/or AP-1 binding sites) in the gene promoter contexts. In addition, altered expression profiles of some Wnt/β-catenin signaling proteins were context dependent, as accompanied by decreased abundances of Nrf1 in the clinic human hepatomas with distinct differentiation. Together, these results corroborate the rationale that Nrf1 acts as a bona fide dominant tumor repressor, by its intrinsic inhibition of Wnt/β-catenin signaling and relevant independent networks in cancer development and malignant progression."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Exosomes for Diagnosis and Therapy in Gastrointestinal Cancers. (PubMed, Int J Mol Sci) - "In particular, for gastrointestinal cancers, the Frizzled protein involved in those mechanisms is Frizzled-10 (FZD-10). Currently, increasing attention is being devoted to the protein and lipid composition of exosomes interior and membranes, representing profound knowledge of specific exosomes composition fundamental for their application as new delivering drug tools for cancer therapy. This review intends to cover the most recent literature on the use of exosome vesicles for early diagnosis, follow-up, and the use of these physiological nanovectors as drug delivery systems for gastrointestinal cancer therapy."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

RNA Sequencing Reveals the Activation of Wnt Signaling in Low Flow Rate Brain Arteriovenous Malformations. (PubMed, J Am Heart Assoc) - "Experimentally elevating these genes promoted human umbilical vein endothelial cells and migration and tube formation by activating canonical Wnt signaling in vitro. Conclusions Our results suggest that canonical Wnt signaling mediated by FZD 10 and MYOC is activated in vascular endothelial and smooth muscle cells in LFR bAVM s."

Journal • CNS Disorders • Giant Cell Arteritis • Hematological Disorders

A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial-Mesenchymal Transition in Normal Colon Epithelial Cell Line. (PubMed, Int J Mol Sci) - "The exosomes derived from the metastatic cell line, characterized by a level of FZD10 higher than the exosomes extracted from the non-metastatic cells, were also more efficient in stimulating EMT activation. The overall results suggest that FZD10, delivered by circulating tumor-derived exosomes, can play a relevant role in promoting the CRC carcinogenesis and propagation."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

Targeting fatty acid synthase sensitizes human nasopharyngeal carcinoma cells to radiation via downregulating frizzled class receptor 10. (PubMed, Cancer Biol Med) - "Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients. EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs."

Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • FASN

Infection-induced signals generated at the plasma membrane epigenetically regulate Wnt signaling in vitro and in vivo. (PubMed, J Biol Chem) - "Elevated miR-153-3p levels correlated with LRP5/6 and FZD10, and miR-153-3p sequestration via plasmid-based miR-inhibitor system attenuated Wnt signaling. We conclude that infection-induced signals from the plasma membrane epigenetically regulate Wnt signaling."

Journal • Colon Cancer • Colorectal Cancer • Dyslipidemia • Gastrointestinal Cancer • Immune Modulation • Immunology • Infectious Disease • Inflammation

METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP. (PubMed, Cell Biol Int) - "Furthermore, METTL3 knockdown also reduced m6A enrichment of the genes associated with ovarian cancer including EIF3C, AXL, CSF-1, FZD10 in TOV-112D and CRL-11731D cells by RIP-qPCR assay...Taken together, the high expressed METTL3 indicated poor malignancy and survival of EEOC via modulating the aberrant m6A RNA methylation. METTL3-mediated m6A modification, independent of WTAP and METTL14, was considered as a novel mechanism underlying m6A modulation and a potential therapeutic target of EEOC."

Journal • Oncology • Ovarian Cancer • Solid Tumor • Wilms Tumor • AXL • CSF1 • WT1

Mechanism of miRNA-based Aconitum leucostomum Worosch. Monomer inhibition of bone marrow-derived dendritic cell maturation. (PubMed, Int Immunopharmacol) - "Additionally, miR-511-3p downstream targets Calcr, Fzd10, and Eps8, were closely related to BMDCs maturation. DLTD may induce BMDCs maturity through regulation of miRNAs that affect Calcr, Fzd10, and Eps8 gene signals."

Journal • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL6

FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord. (PubMed, PLoS One) - "However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6."

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Lipolysis by downregulating miR-92a activates the Wnt/β-catenin signaling pathway in hypoxic rats. (PubMed, Biomed Rep) - "The increase in the mRNA and protein expression levels of Fzd10 and c-Myc may be associated with miR-92a downregulation. Downregulation of miR-92a in-turn may result in lipolysis through the regulation of the Wnt/β-catenin signaling pathway, and thus weight loss in the rats."

Journal • Preclinical • Metabolic Disorders • MYC

Host Genetic and Gut Microbial Signatures in Familial Inflammatory Bowel Disease. (PubMed, Clin Transl Gastroenterol) - "This study identified familial IBD-associated rare deleterious variants and gut microbial dysbiosis in familial IBD."

Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Psychiatry • LAMA5

Expression of Wnt pathway molecules is associated with disease outcome in metastatic high-grade serous carcinoma. (PubMed, Virchows Arch) - "mRNA expression by qPCR of 20 molecules related to Wnt signaling (WNT1, WNT2, WNT3, WNT4, WNT5A, WNT6, WNT7, WNT11, FZD1, FZD4, FZD5, FZD6, FZD7, FZD8, FZD10, LRP5, LRP6, DKK, CCND, RUNX2) was analyzed in 87 HGSC effusions...In conclusion, expression of Wnt pathway molecules is anatomic site dependent. In HGSC effusions, it is informative of chemoresponse and survival."

Journal • Oncology

Effectiveness of a Controlled 5-FU Delivery Based on FZD10 Antibody-Conjugated Liposomes in Colorectal Cancer In vitro Models. (PubMed, Pharmaceutics) - "The results highlighted that the cytotoxic activity of 5-FU was enhanced when encapsulated in the anti-FZD10 /5-FU/LPs at the lowest tested concentrations, as compared to the free 5-FU counterparts. The immuno-liposomes proposed herein possess a great potential for selective treatment of CRC because, in future clinical applications, they can be encapsulated in gastro-resistant capsules or suppositories for oral or rectal delivery, thereby successfully reaching the intestinal tract in a minimally invasive manner."

Journal • Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

[VIRTUAL] Exploring the Cancer Genome Atlas (TCGA) for the molecular profile of young onset colorectal cancers. (ASCO 2020) - "Patients with YO CRC are more likely to have somatic mutations in genes involved in the MMR pathway and the PI3K/AKT/mTOR pathway. Specifically, in MSH2, MSH6, ATM, FZD10, ERBB2, PIK3R1, PTEN and TGFBR2. When including proteomic data, significant differences were only seen in expression of MSH2/6."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • MSH2 • MSH6 • MSI • PIK3R1 • PTEN

EXPLORING THE CANCER GENOME ATLAS (TCGA) FOR THE MOLECULAR PROFILE OF YOUNG ONSET COLORECTAL CANCERS (DDW 2020) - "Patients with early-onset CRC appear to have different mutation profiles. They are more likely to have somatic mutations in genes involved in the DNA mismatch-repair pathway and the PI3K/AKT/mTOR pathway. Specifically, they are more likely to have mutations in the MSH3, MSH6, ATM, FZD10, ERBB2, PIK3R1, PTEN and TGFBR2 genes."

Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ARID1A • BRAF • CTNNB1 • HER-2 • IGF2 • IRS2 • KRAS • MLH1 • MSH2 • MSH3 • MSH6 • MSI • NRAS • PIK3CA • PMS2 • PTEN • SOX9 • TP53

FZD10 Carried by Exosomes Sustains Cancer Cell Proliferation. (PubMed, Cells) - "Concomitantly, a significant decrease in viability of the silenced cells compared to their respective controls was observed. Notably, the incubation of silenced cells with the exosomes extracted from culture medium of the same untreated cells promoted the restoration of the cell viability and, also, of the FZD10 and FZD10-mRNA level, thus indicating that the FZD10 and FZD10-mRNA delivering exosomes may be potential messengers of cancer reactivation and play an active role in long-distance metastatization."

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N6-methylation of adenosine (m6A) of FZD10 mRNA contributes to PARP inhibitor resistance. (PubMed, Cancer Res) - "Overall, our results show that m6A contributes to PARPi resistance in BRCA-deficient EOC cells by upregulating the Wnt/β-catenin pathway via stabilization of FZD10. They also suggest that inhibition of the Wnt/β-catenin pathway represents a potential strategy to overcome PARPi resistance."

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