scholarly journals Vorolanib, a novel tyrosine receptor kinase receptor inhibitor with potent preclinical anti-angiogenic and anti-tumor activity

Author(s):  
Chris Liang ◽  
Xiaobin Yuan ◽  
Zhilin Shen ◽  
Yang Wang ◽  
Lieming Ding
2020 ◽  
Vol 124 (2) ◽  
pp. 536-543 ◽  
Author(s):  
Mariam Charkviani ◽  
Nino Muradashvili ◽  
Nurul Sulimai ◽  
David Lominadze

For the first time we showed that fibrinogen (Fg) can associate with cellular prion protein (PrPC) on the surface of cultured mouse brain astrocytes. At high levels, Fg causes upregulation of astrocyte PrPC and astrocyte activation accompanied with overexpression of tyrosine receptor kinase B (TrkB), which results in nitric oxide (NO) production and generation of reactive oxygen species (ROS). Fg/PrPC interaction can be a triggering mechanism for TrkB-NO-ROS axis activation and the resultant astrocyte-mediated neurodegeneration.


2018 ◽  
Vol 32 (3) ◽  
pp. 367-372 ◽  
Author(s):  
Munir Gunes Kutlu ◽  
Robert D Cole ◽  
David A Connor ◽  
Brendan Natwora ◽  
Thomas J Gould

2017 ◽  
Vol 66 ◽  
pp. S29
Author(s):  
Aditi Dubey ◽  
Ritu Sehgal ◽  
Ashutosh Kumar ◽  
T.C. Nag ◽  
S. Anurag ◽  
...  

2016 ◽  
Vol 19 (1) ◽  
pp. 22-30 ◽  
Author(s):  
Jing Ni ◽  
Shaozhen Xie ◽  
Shakti H. Ramkissoon ◽  
Victor Luu ◽  
Yu Sun ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6194
Author(s):  
Prachi Mishra ◽  
Dipranjan Laha ◽  
Robert Grant ◽  
Naris Nilubol

Thyroid cancer is the most common type of endocrine malignancy comprising 2–3% of all cancers, with a constant rise in the incidence rate. The standard first-line treatments for thyroid cancer include surgery and radioactive iodine ablation, and a majority of patients show a good response to these therapies. Despite a better response and outcome, approximately twenty percent of patients develop disease recurrence and distant metastasis. With improved knowledge of molecular dysregulation and biological characteristics of thyroid cancer, the development of new treatment strategies comprising novel targets has accelerated. Biomarker-driven targeted therapies have now emerged as a trend for personalized treatments in patients with advanced cancers, and several multiple receptor kinase inhibitors have entered clinical trials (phase I/II/III) to evaluate their safety and efficacy. Most extensively investigated and clinically approved targeted therapies in thyroid cancer include the tyrosine receptor kinase inhibitors that target antiangiogenic markers, BRAF mutation, PI3K/AKT, and MAPK pathway components. In this review, we focus on the current advances in targeted mono- and combination therapies for various types of thyroid cancer.


2021 ◽  
Author(s):  
Brittany M. Smith ◽  
Jake VanCampen ◽  
Garth L. Kong ◽  
William Yashar ◽  
Yiu H. Tsang ◽  
...  

AbstractActivating mutations in the KIT tyrosine receptor kinase confer an adverse prognosis for patients with acute myeloid leukemia (AML). Outside of bone marrow transplantation, treatment options are limited. Here we demonstrate combined KIT and LSD1 inhibition produces synergistic cell death against KIT mutant AML cells. This combination suppresses MYC expression to drive cell cycle exit and apoptosis. This decreased MYC expression results from a loss of PU.1 binding at downstream MYC enhancers. The drug combination also inactivates PI3K/AKT/GSK3a/b signaling to decrease MYC protein abundance. KIT-mutant AML cells rapidly adapt to KIT inhibitor monotherapy by restoring PI3K/AKT activity, but cannot when treated with combined KIT and LSD1 inhibitor. In addition, we validate MYC suppression as a mechanism of synergy in KIT-mutant AML patient samples. Collectively, this work provides rational for a clinical trial to assess the efficacy of KIT and LSD1 inhibition in patients with KIT-mutant AML.Statement of significanceEffective treatment options for AML are limited. We describe the synergistic response to combined KIT and LSD1 inhibition in KIT-mutant AML and identify key biomarkers of drug response. The specificity and efficacy of this combination in cell lines and patient samples provides rationale for investigation in early phase clinical trials.


2017 ◽  
Vol 79 (9) ◽  
pp. 1516-1523 ◽  
Author(s):  
Kosuke OTANI ◽  
Muneyoshi OKADA ◽  
Hideyuki YAMAWAKI

2020 ◽  
Vol 225 (9) ◽  
pp. 2615-2642
Author(s):  
Shoko Takemura ◽  
Ayami Isonishi ◽  
Tatsuhide Tanaka ◽  
Hiroaki Okuda ◽  
Kouko Tatsumi ◽  
...  

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