scholarly journals Recent Advances in the Therapeutic Development of Receptor Tyrosine Kinases (RTK) against Different Types of Cancer

2021 ◽  
Author(s):  
Somi Patranabis
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Therapeutic Strategies ◽  
Cellular Functions ◽  
Recent Advances ◽  
Different Types ◽  
Therapeutic Development ◽  
Potential Applications ◽  
Specific Ligand ◽  
Novel Therapeutic

Receptor Tyrosine Kinases (RTKs) are an important class of receptors involved in regulating different cellular functions. The usual pathway of RTK activation involves specific ligand binding, dimerization and trans-autophosphorylation. Recently, RTK has been extensively studied as they have potential applications in targeted cancer therapy. RTK-based therapeutic strategies are promising because dysfunction of RTK is connected to a variety of diseases. More specifically, RTK has been widely associated with different types of cancer and related diseases. The chapter aims to cover recent advances and challenges in RTK related research, to get an overview of the problems and possibilities associated with targeted therapy. This will help in deciphering novel therapeutic applications in the future.

scholarly journals Steps in Mechanotransduction Pathways that Control Cell Morphology

2019 ◽  
Vol 81 (1) ◽  
pp. 585-605 ◽  
Author(s):  
Haguy Wolfenson ◽  
Bo Yang ◽  
Michael P. Sheetz
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Control Cell ◽  
Matrix Composition ◽  
Cell Behavior ◽  
Repeated Testing ◽  
Cellular Functions ◽  
Rigidity Sensing ◽  
Controlled Environments

It is increasingly clear that mechanotransduction pathways play important roles in regulating fundamental cellular functions. Of the basic mechanical functions, the determination of cellular morphology is critical. Cells typically use many mechanosensitive steps and different cell states to achieve a polarized shape through repeated testing of the microenvironment. Indeed, morphology is determined by the microenvironment through periodic activation of motility, mechanotesting, and mechanoresponse functions by hormones, internal clocks, and receptor tyrosine kinases. Patterned substrates and controlled environments with defined rigidities limit the range of cell behavior and influence cell state decisions and are thus very useful for studying these steps. The recently defined rigidity sensing process provides a good example of how cells repeatedly test their microenvironment and is also linked to cancer. In general, aberrant extracellular matrix mechanosensing is associated with numerous conditions, including cardiovascular disease, aging, and fibrosis, that correlate with changes in tissue morphology and matrix composition. Hence, detailed descriptions of the steps involved in sensing and responding to the microenvironment are needed to better understand both the mechanisms of tissue homeostasis and the pathomechanisms of human disease.

scholarly journals Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ana S. Guerreiro Stucklin ◽  
Scott Ryall ◽  
Kohei Fukuoka ◽  
Michal Zapotocky ◽  
Alvaro Lassaletta ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Therapeutic Strategies ◽  
Low Grade ◽  
High Grade ◽  
Term Survival ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.

scholarly journals Acute Myeloid Leukemia: Focus on novel Therapeutic Strategies

2012 ◽  
Vol 6 ◽  
pp. CMO.S7244 ◽  
Author(s):  
Tara L. Lin ◽  
M. Yair Levy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Risk Groups ◽  
The Elderly ◽  
Therapeutic Strategies ◽  
Recent Advances ◽  
Novel Therapeutic Strategies ◽  
Acute Myeloid ◽  
Novel Therapeutic

Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed in the induction, post-remission and relapsed settings. The additions of clofarabine for relapsed or refractory disease and the hypomethylating agents represent recent advances. Clinical trials of FLT3 inhibitors have yielded disappointing results to date, with ongoing collaborations attempting to identify the optimal role for these agents. Potential leukemia stem cell targeted therapies and treatments in the setting of minimal residual disease are also under investigation. In this review, we will discuss recent advances in AML treatment and novel therapeutic strategies.

scholarly journals Recent advances in the regulation of cholangiocarcinoma growth

2010 ◽  
Vol 299 (1) ◽  
pp. G1-G9 ◽  
Author(s):  
Heather Francis ◽  
Gianfranco Alpini ◽  
Sharon DeMorrow
Keyword(s):  
Neoplastic Transformation ◽  
Therapeutic Strategies ◽  
Chemotherapeutic Agents ◽  
Biliary Epithelium ◽  
Recent Advances ◽  
Relative Rarity ◽  
Deadly Disease ◽  
Novel Therapeutic Strategies ◽  
Molecular Pathophysiology ◽  
Novel Therapeutic

Cholangiocarcinomas arise after the neoplastic transformation of the cholangiocytes that line the intra- and extrahepatic biliary epithelium. Symptoms usually do not present until late in the course of the disease, at which time they are relatively resistant to chemotherapeutic agents and as such are difficult to treat and display a poor prognosis. Because of the relative rarity of this disease, the overall volume of research into the molecular pathophysiology associated with this disease is small compared with other more prevalent tumors. However, the incidence of this devastating cancer is on the rise and renewed efforts to understand the pathogenesis of cholangiocarcinoma is needed to design novel therapeutic strategies to combat this disease. This review summarizes the recent advances into our knowledge and understanding of cholangiocarcinoma and highlights potential novel therapeutic strategies that may prove useful to treat this deadly disease.

MET and RON Receptor Tyrosine Kinases: Novel Therapeutic Targets in Squamous Cell Carcinoma of the Head and Neck

2007 ◽  
Vol 3 (1) ◽  
pp. 1-12
Author(s):  
Susanne Rogers ◽  
Carol Box ◽  
Christopher Nutting ◽  
Peter Rhys Evans ◽  
Kevin Harrington ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Therapeutic Targets ◽  
Ron Receptor ◽  
Novel Therapeutic

scholarly journals The Roles of Extracellular Vesicles in Malignant Melanoma

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2740
Author(s):  
Ying-Chen Cheng ◽  
Yu-An Chang ◽  
Yi-Jen Chen ◽  
Hsu-Min Sung ◽  
Ivan Bogeski ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Endothelial Cells ◽  
Malignant Melanoma ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Therapeutic Strategies ◽  
Bioactive Molecules ◽  
Different Types ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.

scholarly journals Utilization of Glycosaminoglycans/Proteoglycans as Carriers for Targeted Therapy Delivery

2015 ◽  
Vol 2015 ◽  
pp. 1-25 ◽  
Author(s):  
Suniti Misra ◽  
Vincent C. Hascall ◽  
Ilia Atanelishvili ◽  
Ricardo Moreno Rodriguez ◽  
Roger R. Markwald ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Therapeutic Strategies ◽  
Extracellular Matrices ◽  
Cancer Tissue ◽  
Tissue Architecture ◽  
Patients With Cancer ◽  
The Past ◽  
Invasive Behavior ◽  
Therapy Delivery

The outcome of patients with cancer has improved significantly in the past decade with the incorporation of drugs targeting cell surface adhesive receptors, receptor tyrosine kinases, and modulation of several molecules of extracellular matrices (ECMs), the complex composite of collagens, glycoproteins, proteoglycans, and glycosaminoglycans that dictates tissue architecture. Cancer tissue invasive processes progress by various oncogenic strategies, including interfering with ECM molecules and their interactions with invasive cells. In this review, we describe how the ECM components, proteoglycans and glycosaminoglycans, influence tumor cell signaling. In particular this review describes how the glycosaminoglycan hyaluronan (HA) and its major receptor CD44 impact invasive behavior of tumor cells, and provides useful insight when designing new therapeutic strategies in the treatment of cancer.

scholarly journals Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand–receptor interactions

2015 ◽  
Vol 112 (52) ◽  
pp. 15862-15867 ◽  
Author(s):  
Andrey V. Reshetnyak ◽  
Phillip B. Murray ◽  
Xiarong Shi ◽  
Elizabeth S. Mo ◽  
Jyotidarsini Mohanty ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Orphan Receptor ◽  
3T3 Cells ◽  
Cellular Functions ◽  
Surface Receptors ◽  
Anaplastic Lymphoma ◽  
Disease States ◽  
Receptor Interactions ◽  
Nih 3T3

Receptor tyrosine kinases (RTKs) are a class of cell surface receptors that, upon ligand binding, stimulate a variety of critical cellular functions. The orphan receptor anaplastic lymphoma kinase (ALK) is one of very few RTKs that remain without a firmly established protein ligand. Here we present a novel cytokine, FAM150B, which we propose naming augmentor-α (AUG-α), as a ligand for ALK. AUG-α binds ALK with high affinity and activates ALK in cells with subnanomolar potency. Detailed binding experiments using cells expressing ALK or the related receptor leukocyte tyrosine kinase (LTK) demonstrate that AUG-α binds and robustly activates both ALK and LTK. We show that the previously established LTK ligand FAM150A (AUG-β) is specific for LTK and only weakly binds to ALK. Furthermore, expression of AUG-α stimulates transformation of NIH/3T3 cells expressing ALK, induces IL-3 independent growth of Ba/F3 cells expressing ALK, and is expressed in neuroblastoma, a cancer partly driven by ALK. These experiments reveal the hierarchy and specificity of two cytokines as ligands for ALK and LTK and set the stage for elucidating their roles in development and disease states.

scholarly journals Prognostic and Clinicopathologic Significance of Discoidin Domain Receptors in Different Human Malignancies: A Meta-Analysis

2021 ◽  
pp. 1-10
Author(s):  
Gordon A. Ferns ◽  
Sheida Shabanian ◽  
Milad Shahini Shams Abadi ◽  
Ahmadshah Farhat ◽  
Mohammad-Hassan Arjmand
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Meta Analysis ◽  
Cancer Type ◽  
Prognostic Effect ◽  
Discoidin Domain Receptors ◽  
Physiological Processes ◽  
Urological Cancers ◽  
Different Types ◽  
English Articles

<b><i>Background:</i></b> Discoidin domain receptors (DDRs) belong to the receptor tyrosine kinases family and are activated by different types of collagens, which play roles in various physiological processes. An abnormal expression of DDRs is reported in different types of cancers. Despite many reports about the association and roles of high DDR expression levels in cancers, the prognostic values of DDRs are still unclear. This meta-analysis was performed to evaluate the prognostic effect of DDRs in different tissue cancers. <b><i>Method:</i></b> A literature search was performed in several related databases to find eligible English articles. Based on our research, 20 appropriate studies with 2,602 patients were selected till October 5, 2020. The pooled hazard ratio (HR) with a corresponding 95% confidence interval (CI) was computed to evaluate the strength of correlation between DDRs and survival of cancer patients. <b><i>Result:</i></b> Pooling results showed that a high DDR expression was significantly associated with poorer overall survival (OS) (HR = 1.304, 95% CI 1.007–1.69, <i>p</i> = 0.04). Subgroup analysis based on cancer type revealed a significant link between a high DDR expression level and poor OS both in gastrointestinal (pooled HR = 1.78, 95% CI 1.214–2.624, <i>p</i> = 0.003) and urological cancers (pooled HR = 1.42, 95% CI 1.062–1.82, <i>p</i> = 0.018). <b><i>Conclusion:</i></b> Our meta-analysis results suggest that high DDRs expression has the potential to be used as a biomarker of poor prognosis in cancers.

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