مقالات پذیرفته شده در هفتمین کنگره بین المللی زیست پزشکی
Investigate function of Wnt/Β-Catenin Signaling Pathways in Cancer
Investigate function of Wnt/Β-Catenin Signaling Pathways in Cancer
Sahar Eskandari,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran
Introduction: Introduction: Genetic changes are the basic cause of the disease of cancer. The Wnt/-catenin signaling pathway is linked to the control of stem cell pluripotency, self-renewal, and differentiation potential. The Wnt/-catenin pathway is abnormally activated in cancer, which promotes tumor growth, degeneration, and metastasis. A conserved signaling axis involved in a variety of physiological processes, including proliferation, differentiation, apoptosis, migration, invasion, and tissue homeostasis, is the Wnt/-catenin signaling system, also known as the canonical Wnt signaling pathway. There is growing evidence that certain solid tumors and hematological malignancies were able to originate and progress because of disruption of the Wnt/-catenin cascade. This review study aimed to Investigate the function of Wnt/Β-Catenin Signaling Pathways in Cancer.
Methods: Search Method: The current study was conducted by scanning scholarly resources such as Google Scholar, Science Direct, Springer, and PubMed for information on investigating the function of Wnt/Β-Catenin Signaling Pathways in Cancer
Results: Results: Several co-activators of -catenin-dependent transcription, including CREB binding protein (CBP), are involved in the signaling pathways in various forms of cancer, according to the findings of numerous studies on these pathways. The CBPs are important transcriptional co-activators necessary for numerous cellular functions, as well as being involved in cancer and pathological states in humans. Recent years have seen the development of several CBP inhibitors, some of which have demonstrated positive antineoplastic benefits in preclinical animals with little off-target effects. These inhibitors include PRI-724, ICG001, GNE-781, 1-(1H-indol-1-yl) ethenone, JW67, JW74, NLS-StAx-h, and others. A ground-breaking small molecule antagonist, PRI-724 prevents the interaction between -catenin and CBP. It was promptly hydrolyzed to its active form, C-82, in vivo after being phosphorylated. Preclinical research had demonstrated a significant toxicity profile and PRI-724 elevated sensitization to platinum treatment in chemotherapy-resistant EOC with hyperactivated CBP/-catenin pathway. ICG-001 monotherapy resulted in a decrease in tumor-related features. In an acute myeloid leukemia (AML) model, GNE-781 demonstrated anti-tumor action. It was also demonstrated that Foxp3 transcript levels decreased in a dose-dependent way. In multiple prostate cancer cell lines, 1-(1H-indol-1-yl) ethenone significantly reduced cell proliferation. JW67 and JW74 were found to specifically inhibit the canonical Wnt pathway at the level of the destruction complex, preventing the development of various intestinal neoplasia animals and colorectal cancer mouse xenograft models
Conclusion: Conclusions: in Conclusions Novel strategies are imperative to improve the outcome of cancer patients. With great advances in the knowledge of molecular basis and the constant effort for improvement, preclinical investigations and clinical trials have been conducted on the Wnt/β-catenin signaling targeted interventions in malignancies. The Wnt/β-catenin signaling targeted regimens have been proven to represent promising candidates for individualized approaches in the treatment of cancer patients. Further investigations are expected to confirm the safety, efficacy, patient stratification and drug delivery of innovative Wnt/β-catenin targeted therapies in cancer.