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Targeted Therapy for Cancer Stem Cells
Published in Surinder K. Batra, Moorthy P. Ponnusamy, Gene Regulation and Therapeutics for Cancer, 2021
Rama Krishna Nimmakayala, Saswati Karmakar, Garima Kaushik, Sanchita Rauth, Srikanth Barkeer, Saravanakumar Marimuthu, Moorthy P. Ponnusamy
Notch signaling played a role in cell-cell communication and was found to be essential for cell proliferation and apoptosis during embryonic development. Several pathways such as nuclear factor-xB (NF-xB), HH, mammalian target of rapamycin (mTOR), Wnt, and epidermal growth factor have been shown to cross-talk with notch pathway, and thus, play significant functions in CSCs and tumor growth [69–71]. Therefore, Notch can be an attractive therapeutic target for CSCs treatment. Therapeutics aiming Notch signaling mainly consist of anti-Delta-like ligand 4 (DLL4) antibodies and g-secretase inhibitors. The main function of monoclonal antibodies against DLL4 is to block the binding of a ligand. Encticumab (REN421) is a DLL4 targeting antibody and has been used to treat advanced ovarian solid tumors overexpressing DLL4 [72]. Demcizumab is another anti-DLL4 antibody developed by OncoMed Pharmaceuticals and Celgene, and has completed the phase I clinical trial. In addition to inhibitors against DLL4, various g-secretase inhibitors such as RO4929097 and LY900009 have been undergoing phase I trial. RO4929097 suppresses Notch signaling genes, such as Hey1, Hey L and Hes1, thus blocking activation of self-renewal genes [10].
Function and mechanism exploration of zinc finger protein 64 in lung adenocarcinoma cell growth and metastasis
Published in Journal of Receptors and Signal Transduction, 2021
Jiuyang Jiang, Jian Zhang, Kai Fu, Tiewa Zhang
The Notch signaling system is the crucial fundamental pathway, a unique cellular program, which acts a key role in cell development and differentiation [7]. Aberrant activation of Notch signaling pathway has been discovered in a variety of solid tumors can lead to cell proliferation, metastasis as well as EMT progress [8]. For instance, Notch‐1 and Notch‐2 were shown to play the important roles in colorectal cancer, which were involved in its tumorigenesis and progression, and Notch‐3 was also demonstrated to be promoted in metastatic colorectal cancer [9,10]. Moreover, Carvalho et al. [11] found that Notch signaling can antagonize benign and malignant prostate cells growth and survival via targeting HEY1. Importantly, Notch signaling had been proved that it was related to worse outcome in patients with lung adenocarcinoma, indicating that inhibition of Notch activity could be a potential therapeutic method for lung adenocarcinoma treatment [12]. In addition, KRAB zinc finger protein 382 had been reported to play an important role of inhibiting tumor progression in gastric cancer, and it could reverse the EMT process in gastric cancer cells through Notch signaling pathway, suggesting that ZFPs might be involved in tumor progression via regulating Notch signaling pathway [13]. Importantly, ZFP64 has been discovered to mediate mesenchymal cell differentiation by modulating Notch signaling [14].
The Notch pathway: a novel therapeutic target for cardiovascular diseases?
Published in Expert Opinion on Therapeutic Targets, 2019
Giorgio Aquila, Aleksandra Kostina, Francesco Vieceli Dalla Sega, Eugeniy Shlyakhto, Anna Kostareva, Luisa Marracino, Roberto Ferrari, Paola Rizzo, Anna Malaschicheva
The sequential expression of components of the Notch pathways and related genes is indispensable during the development of heart and vessels. The role of Notch in the cardiovascular development has been deeply investigated and its discussion is beyond the scope of this review: we give here a brief overview of the field, to set the stage for our discussion of the role of Notch in cardiovascular disease, and refer the reader to several excellent reviews for details [25–27]. Notch ligands and receptors are sequentially expressed in the developing heart, thus ensuring proper heart development. Notch ligand Jagged1 is expressed very early during heart development, labeling the presumptive valve area of the atrioventricular channel (AVC) and the trabecular myocardium, while ligand Dll4 and receptors Notch2 and Notch4 are expressed in the endocardium. Then, Dll4 expression decreases whereas Jagged1 expression is maintained in the endocardium and is activated in the compacted myocardium [25,28]. This sequential expression of Notch genes Jagged1, Dll4, Notch2 and Notch4 supports myocardial patterning, maturation and compaction and cardiac trabeculae formation [25,28]. The Notch pathway plays an important role in the development of outflow tract (OFT) of the heart which starts with endothelial-to-mesenchymal transition (EMT) in the endocardial cells leading to the formation of cardiac valves. The involvement of Notch1 in this context is indicated by the expression of this receptor in prospective valve endocardium at the beginning of EMT [29]. Consistently with the importance of Notch in the developing heart, mice lacking Notch target genes Hey1 and Hey2 die during embryogenesis due to severe cardiovascular malformations, including impaired development of EMT [30].
Robot-assisted radical nephrectomy for primary renal mesenchymal chondrosarcoma: case report and literature review
Published in Renal Failure, 2019
Wen Deng, Jinxiu Zhou, Xiaoqiang Liu, Luyao Chen, Guanghua Guo, Bin Fu
Many new treatment strategies have been introduced. Shakked et al. [26] introduced therapies targeting the platelet-derived growth factor receptor α proliferation pathway may be beneficial in treating MC. de Jong et al. [27] reported that the inhibition of Bcl-2 family members sensitizes MC to conventional chemotherapy, which provides new methods for treating MC. Many studies have implied that HEY1-NCOA2 rearrangement is not only a diagnostic marker but also a potential therapeutic promoter for MC [28,29]. However, all these new opinions need further verification.