The in vitro and in vivo validation demonstrated that SXP-NPs offer several advantages, including high drug-loading potential, broad-spectrum recognition of leukemia cells, reduced systemic toxicity, and enhanced therapeutic effects of the drug. Taken together, this study provides a simple and effective strategy for broad-spectrum leukemia therapy and highlights the clinical potential of SXP-NPs.
PTK7 has been identified as a potential therapeutic target, and a PTK7 antibody drug conjugate (PF-06647020; cofetuzumab pelidotin) has been investigated in phase I clinical trials for triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer...PTK7 protein and mRNA expression were associated with breast cancer-specific survival of patients with a poor prognostic Nottingham Prognostic Index (NPI) and a moderate prognostic NPI, respectively. Taken together, these data indicate that PTK7 expression is associated with patient outcome in subgroups of breast cancer patients.
Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.
PTK7 expression induced by oxaliplatin (OXA) uptake was assayed with LIF, while ICP-MS measurement of 195Pt revealed OXA uptake of the drug in individual cells, which provided further in-depth information about the drug in relation to PTK7 expression...Using a machine learning algorithm to initially profile drug uptake and marker expression in tumor cell lines, μCytoMS was able to perform in situ profiling of the PTK7 response to the OXA at single-cell resolution for tests done on clinical samples from 10 breast cancer patients. It offers great potential for multiplex single-cell phenotypic analysis and clinical diagnosis.
Furthermore, deactivation of FAK using siFAK or FAK inhibitor (PF-573228, PF) synergistically contributed to PTK7 knockdown-inhibited FAK activity, MMP7 expression, and the migration and invasion abilities of HCC cells. Collectively, our findings show that PTK7 mediates HCC progression by regulating the MTA2-FAK-MMP7 axis and may be a diagnostic value for HCC patients.
1 year ago
Journal
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PTK7 (Protein Tyrosine Kinase 7) • MTA2 (Metastasis Associated 1 Family Member 2) • MMP7 (Matrix metallopeptidase 7)
Although the TROP2-targeting ADC sacituzumab govitecan was recently granted accelerated approval from the FDA for treating patients with metastatic TNBC,1 the on-target toxicity of this single-targeting agent has limited clinical efficacy. Conclusions BCG033 is a novel bispecific antibody-drug conjugate that targets PTK7 and TROP2. BCG033 demonstrates promising preclinical efficacy in vivo, suggesting it may offer new treatment options for TNBC or other solid tumors expressing PTK7 and TROP2 in the future.