scholarly journals Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers in Meningioma

2021 ◽  
Author(s):  
Rafael Roesler ◽  
Barbara Kunzler Souza ◽  
Gustavo R. Isolan
Keyword(s):  
Tyrosine Kinases ◽  
Clinical Evidence ◽  
Growth Factor Receptor ◽  
Prognostic Biomarkers ◽  
Clinical Prognosis ◽  
Erbb Family ◽  
The Past ◽  
Cancer Types ◽  
Epidermal Growth

Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets. The role of receptor tyrosine kinase (RTKs), including those of the ErbB family of receptors, as oncogenes has been well established in several cancer types. Here, we review histological, molecular, and clinical evidence suggesting that RTKs, including the epidermal growth factor receptor (EGFR, ErbB 1), as well as other members of the ErbB family, may be useful as biomarkers in MGM.

scholarly journals Receptor Tyrosine Kinases as Candidate Prognostic Biomarkers and Therapeutic Targets in Meningioma

2021 ◽  
Vol 22 (21) ◽  
pp. 11352
Author(s):  
Rafael Roesler ◽  
Barbara Kunzler Souza ◽  
Gustavo R. Isolan
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Therapeutic Targets ◽  
Growth Factor Receptor ◽  
Prognostic Biomarkers ◽  
Clinical Prognosis ◽  
Erbb Family ◽  
Cancer Types ◽  
Epidermal Growth

Meningioma (MGM) is the most common type of intracranial tumor in adults. The validation of novel prognostic biomarkers to better inform tumor stratification and clinical prognosis is urgently needed. Many molecular and cellular alterations have been described in MGM tumors over the past few years, providing a rational basis for the identification of biomarkers and therapeutic targets. The role of receptor tyrosine kinases (RTKs) as oncogenes, including those of the ErbB family of receptors, has been well established in several cancer types. Here, we review histological, molecular, and clinical evidence suggesting that RTKs, including the epidermal growth factor receptor (EGFR, ErbB1), as well as other members of the ErbB family, may be useful as biomarkers and therapeutic targets in MGM.

scholarly journals An Electrostatic Engine Model for Autoinhibition and Activation of the Epidermal Growth Factor Receptor (EGFR/ErbB) Family

2005 ◽  
Vol 126 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Stuart McLaughlin ◽  
Steven O. Smith ◽  
Michael J. Hayman ◽  
Diana Murray
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinases ◽  
Structural Model ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Correlation Spectroscopy ◽  
Erbb Family ◽  
Epidermal Growth

We propose a new mechanism to explain autoinhibition of the epidermal growth factor receptor (EGFR/ErbB) family of receptor tyrosine kinases based on a structural model that postulates both their juxtamembrane and protein tyrosine kinase domains bind electrostatically to acidic lipids in the plasma membrane, restricting access of the kinase domain to substrate tyrosines. Ligand-induced dimerization promotes partial trans autophosphorylation of ErbB1, leading to a rapid rise in intracellular [Ca2+] that can activate calmodulin. We postulate the Ca2+/calmodulin complex binds rapidly to residues 645–660 of the juxtamembrane domain, reversing its net charge from +8 to −8 and repelling it from the negatively charged inner leaflet of the membrane. The repulsion has two consequences: it releases electrostatically sequestered phosphatidylinositol 4,5-bisphosphate (PIP2), and it disengages the kinase domain from the membrane, allowing it to become fully active and phosphorylate an adjacent ErbB molecule or other substrate. We tested various aspects of the model by measuring ErbB juxtamembrane peptide binding to phospholipid vesicles using both a centrifugation assay and fluorescence correlation spectroscopy; analyzing the kinetics of interactions between ErbB peptides, membranes, and Ca2+/calmodulin using fluorescence stop flow; assessing ErbB1 activation in Cos1 cells; measuring fluorescence resonance energy transfer between ErbB peptides and PIP2; and making theoretical electrostatic calculations on atomic models of membranes and ErbB juxtamembrane and kinase domains.

scholarly journals ErBb Family Proteins in Cholangiocarcinoma and Clinical Implications

2020 ◽  
Vol 9 (7) ◽  
pp. 2255
Author(s):  
Wook Jin
Keyword(s):  
Cellular Networks ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Clinical Implications ◽  
Tumor Aggressiveness ◽  
Erbb Family ◽  
Constitutive Activation ◽  
Epidermal Growth ◽  
Viral Oncogene Homolog

The erythroblastic leukemia viral oncogene homolog (ErBb) family consists of the receptor tyrosine kinases (RTK) epidermal growth factor receptor (EGFR; also called ERBB1), ERBB2, ERBB3, and ERBB4. This family is closely associated with the progression of cholangiocarcinoma (CC) through the regulation of cellular networks, which are enhanced during tumorigenesis, metastasis, and chemoresistance. Additionally, the constitutive activation of cellular signaling by the overexpression and somatic mutation-mediated alterations conferred by the ErBb family on cholangiocarcinoma and other cancers enhances tumor aggressiveness and chemoresistance by contributing to the tumor microenvironment. This review summarizes the recent findings on the molecular functions of the ErBb family and their mutations during the progression of cholangiocarcinoma. It also discusses the developments and applications of various devising strategies for targeting the ErBb family through different inhibitors in various stages of clinical trials, which are essential for improving targeted clinical therapies.

scholarly journals HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1808
Author(s):  
Carla De Giovanni ◽  
Lorena Landuzzi ◽  
Arianna Palladini ◽  
Giordano Nicoletti ◽  
Patrizia Nanni ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Myogenic Differentiation ◽  
Growth Factor Receptor ◽  
Her Family ◽  
Her2 Mutation ◽  
Epidermal Growth ◽  
Egfr Family

Rhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features allow for distinction between subtypes: morphology and presence/absence of a translocation between the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation with driving activity on tumor growth. HER3 is frequently overexpressed by RMS and can play a role in the residual myogenic differentiation ability and in resistance to signaling-directed therapy. HER family members could be exploited for therapeutic approaches in two ways: blocking the HER member (playing a driving role for tumor growth with antibodies or inhibitors) and targeting expressed HER members to vehiculate toxins or immune effectors.

Development of strategies for the use of anti-growth factor treatments

2005 ◽  
Vol 12 (Supplement_1) ◽  
pp. S173-S182 ◽  
Author(s):  
H E Jones ◽  
J M W Gee ◽  
K M Taylor ◽  
D Barrow ◽  
H D Williams ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
De Novo ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Cancer Cell Proliferation ◽  
Over Expression ◽  
Combination Strategies ◽  
Cancer Types ◽  
Epidermal Growth

Aberrant signalling through the epidermal growth factor receptor (EGFR) is associated with increased cancer cell proliferation, reduced apoptosis, invasion and angiogenesis. Over-expression of the EGFR is seen in a variety of tumours and is a rational target for antitumour strategies. Among the classes of agent targeting the EGFR are small-molecule inhibitors, which include gefitinib (IRESSA™), which acts by preventing EGFR phosphorylation and downstream signal transduction. De novo and acquired resistance, however, have been reported to gefitinib and here we describe evidence which indicates that the type II receptor tyrosine kinases (RTKs) insulin-like growth factor-I receptor (IGF-IR) and/or insulin receptor (InsR) play important roles in the mediation of responses to gefitinib in the de novo- and acquired-resistance phenotypes in several cancer types. Moreover, combination strategies that additionally target the IGF-IR/InsR can enhance the antitumour effects of gefitinib.

scholarly journals Non-catalytic activation of phospholipase C-γ 1 in vitro by epidermal growth factor receptor

1993 ◽  
Vol 293 (2) ◽  
pp. 507-511 ◽  
Author(s):  
S M T Hernández-Sotomayor ◽  
G Carpenter
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase C ◽  
Tyrosine Kinases ◽  
Egf Receptor ◽  
Growth Factor Receptor ◽  
Catalytic Activation ◽  
Epidermal Growth

To investigate the possible functional role of epidermal growth factor (EGF) receptor-phospholipase C-gamma 1 (PLC-gamma 1) complexes, we have measured PLC-gamma 1 activity in vitro in the absence or presence of purified EGF receptor. Immunoprecipitates of PLC-gamma 1 from control A-431 cells were incubated without or with purified EGF receptor in the absence or presence of ATP. Under these conditions the EGF receptor increased non-tyrosine-phosphorylated PLC-gamma 1 activity 3-4-fold in the absence or presence of ATP, but increased tyrosine-phosphorylated and activated PLC-gamma 1 by only 20-50%. Both basal and autophosphorylated forms of the purified EGF receptor increased the activity of the non-tyrosine-phosphorylated PLC-gamma 1, and stoichiometric levels of purified receptor were required to increase PLC activity. Other tyrosine kinases such as the platelet-derived growth factor receptor and erbB-2, but not the insulin receptor, also stimulated PLC-gamma 1 activity. PLC-gamma 1 activity could be activated with the kinase-negative EGF receptor, but a C-terminal truncated receptor was much less effective. Purified EGF receptor could also activate PLC-beta 1, but with a much decreased potency compared with PLC-gamma 1. Our results suggest that in vitro the EGF receptor can increase PLC-gamma 1 activity independently of tyrosine phosphorylation.

scholarly journals Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer

2021 ◽  
Vol 22 (13) ◽  
pp. 6813
Author(s):  
Chiara Guarini ◽  
Teresa Grassi ◽  
Gaetano Pezzicoli ◽  
Camillo Porta
Keyword(s):  
Colorectal Cancer ◽  
Somatic Mutations ◽  
Clinical Evidence ◽  
Advanced Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Predictive Biomarker ◽  
Therapeutic Implications ◽  
Oncogenic Driver ◽  
Epidermal Growth

The human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic driver and a successful therapeutic target in several malignancies, such as breast and gastric cancers. HER2 alterations, including amplification and somatic mutations, have also been detected in a small but not negligible subset of patients affected by advanced colorectal cancer (aCRC). However, to date, there are no available oncotargets in this malignancy beyond RAS and BRAF that are available. Here we present an overview on the present predictive and prognostic role of HER2 expression in aCRC, as well as on its consequent potential therapeutic implications from preclinical investigations towards ongoing trials testing anti-HER2 agents in aCRC. While HER2′s role as a molecular predictive biomarker for anti-EGFR therapies in CRC is recognized, HER2 prognostic value remains controversial. Moreover, thanks to the impressive and growing body of clinical evidence, HER2 is strongly emerging as a new potential actionable oncotarget in aCRC. In conclusion, in the foreseeable future, HER2-targeted therapeutic strategies may integrate the algorithm of aCRC treatment towards an increasingly tailored therapeutic approach to this disease.

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