scholarly journals C-Met as a Key Factor Responsible for Sustaining Undifferentiated Phenotype and Therapy Resistance in Renal Carcinomas

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 272 ◽  
Author(s):  
Paulina Marona ◽  
Judyta Górka ◽  
Jerzy Kotlinowski ◽  
Marcin Majka ◽  
Jolanta Jura ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tumor Growth ◽  
Kinase Inhibitors ◽  
Mesenchymal Cell ◽  
Therapy Resistance ◽  
Cell Phenotype ◽  
Tyrosine Kinase Receptor ◽  
Met Receptor ◽  
Mesenchymal Phenotype

C-Met tyrosine kinase receptor plays an important role under normal and pathological conditions. In tumor cells’ overexpression or incorrect activation of c-Met, this leads to stimulation of proliferation, survival and increase of motile activity. This receptor is also described as a marker of cancer initiating cells. The latest research shows that the c-Met receptor has an influence on the development of resistance to targeted cancer treatment. High c-Met expression and activation in renal cell carcinomas is associated with the progression of the disease and poor survival of patients. C-Met receptor has become a therapeutic target in kidney cancer. However, the therapies used so far using c-Met tyrosine kinase inhibitors demonstrate resistance to treatment. On the other hand, the c-Met pathway may act as an alternative target pathway in tumors that are resistant to other therapies. Combination treatment together with c-Met inhibitor reduces tumor growth, vascularization and pro-metastatic behavior and results in suppressed mesenchymal phenotype and vascular endothelial growth factor (VEGF) secretion. Recently, it has been shown that the acquirement of mesenchymal phenotype or lack of cell differentiation might be related to the presence of the c-Met receptor and is consequently responsible for therapy resistance. This review presents the results from recent studies identifying c-Met as an important factor in renal carcinomas being responsible for tumor growth, progression and metastasis, indicating the role of c-Met in resistance to antitumor therapy and demonstrating the pivotal role of c-Met in supporting mesenchymal cell phenotype.

A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

2020 ◽  
Vol 7 (2) ◽  
pp. 205-211
Author(s):  
Kaynat Fatima ◽  
Syed Tasleem Raza ◽  
Ale Eba ◽  
Sanchita Srivastava ◽  
Farzana Mahdi
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

scholarly journals Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma

2021 ◽  
Vol 14 (7) ◽  
pp. 626
Author(s):  
Julie Bolcaen ◽  
Shankari Nair ◽  
Cathryn H. S. Driver ◽  
Tebatso M. G. Boshomane ◽  
Thomas Ebenhan ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Radionuclide Therapy ◽  
Kinase Inhibitors ◽  
Nuclear Imaging ◽  
Therapy Resistance ◽  
Targeted Radionuclide Therapy ◽  
Therapy Strategy ◽  
Dismal Prognosis

Glioblastoma (GB) remains the most fatal brain tumor characterized by a high infiltration rate and treatment resistance. Overexpression and/or mutation of receptor tyrosine kinases is common in GB, which subsequently leads to the activation of many downstream pathways that have a critical impact on tumor progression and therapy resistance. Therefore, receptor tyrosine kinase inhibitors (RTKIs) have been investigated to improve the dismal prognosis of GB in an effort to evolve into a personalized targeted therapy strategy with a better treatment outcome. Numerous RTKIs have been approved in the clinic and several radiopharmaceuticals are part of (pre)clinical trials as a non-invasive method to identify patients who could benefit from RTKI. The latter opens up the scope for theranostic applications. In this review, the present status of RTKIs for the treatment, nuclear imaging and targeted radionuclide therapy of GB is presented. The focus will be on seven tyrosine kinase receptors, based on their central role in GB: EGFR, VEGFR, MET, PDGFR, FGFR, Eph receptor and IGF1R. Finally, by way of analyzing structural and physiological characteristics of the TKIs with promising clinical trial results, four small molecule RTKIs were selected based on their potential to become new therapeutic GB radiopharmaceuticals.

scholarly journals Potential role of tyrosine kinase inhibitors during primary HIV-1 infection

2017 ◽  
Vol 15 (5) ◽  
pp. 421-423 ◽  
Author(s):  
Juan Ambrosioni ◽  
Mayte Coiras ◽  
José Alcamí ◽  
José M. Miró
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Potential Role ◽  
Kinase Inhibitors ◽  
Hiv 1

scholarly journals Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review

2006 ◽  
Vol 17 (8) ◽  
pp. 1185-1196 ◽  
Author(s):  
P. Schöffski ◽  
H. Dumez ◽  
P. Clement ◽  
A. Hoeben ◽  
H. Prenen ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Cell Cancer ◽  
Advanced Renal Cell Cancer

scholarly journals Immunization against ROS1 by DNA Electroporation Impairs K-Ras-Driven Lung Adenocarcinomas

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 166
Author(s):  
Federica Riccardo ◽  
Giuseppina Barutello ◽  
Angela Petito ◽  
Lidia Tarone ◽  
Laura Conti ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Line ◽  
Kinase Inhibitors ◽  
Immune Memory ◽  
Tyrosine Kinase Receptor ◽  
Preclinical Model ◽  
Primary Tumors ◽  
Improve Patient Survival ◽  
Transplantable Cell ◽  
Lung Adenocarcinomas

Non-small cell lung cancer (NSCLC) is still the leading cause of cancer death worldwide. Despite the introduction of tyrosine kinase inhibitors and immunotherapeutic approaches, there is still an urgent need for novel strategies to improve patient survival. ROS1, a tyrosine kinase receptor endowed with oncoantigen features, is activated by chromosomal rearrangement or overexpression in NSCLC and in several tumor histotypes. In this work, we have exploited transgenic mice harboring the activated K-Ras oncogene (K-RasG12D) that spontaneously develop metastatic NSCLC as a preclinical model to test the efficacy of ROS1 immune targeting. Indeed, qPCR and immunohistochemical analyses revealed ROS1 overexpression in the autochthonous primary tumors and extrathoracic metastases developed by K-RasG12D mice and in a derived transplantable cell line. As proof of concept, we have evaluated the effects of the intramuscular electroporation (electrovaccination) of plasmids coding for mouse- and human-ROS1 on the progression of these NSCLC models. A significant increase in survival was observed in ROS1-electrovaccinated mice challenged with the transplantable cell line. It is worth noting that tumors were completely rejected, and immune memory was achieved, albeit only in a few mice. Most importantly, ROS1 electrovaccination was also found to be effective in slowing the development of autochthonous NSCLC in K-RasG12D mice.

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