scholarly journals Molecular Targeting Therapy against EGFR Family in Breast Cancer: Progress and Future Potentials

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1826 ◽  
Author(s):  
Amaia Eleonora Maennling ◽  
Mehmet Kemal Tur ◽  
Marcus Niebert ◽  
Torsten Klockenbring ◽  
Felix Zeppernick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinases ◽  
Cell Cycle Progression ◽  
Growth Factor Receptor ◽  
Targeting Therapy ◽  
Pancreas Head ◽  
Downstream Signaling ◽  
Strong Stimulation ◽  
Epidermal Growth ◽  
Egfr Family

The epidermal growth factor receptor (EGFR) family contains four transmembrane tyrosine kinases (EGFR1/ErbB1, Her2/ErbB2, Her3/ErbB3 and Her4/ErbB4) and 13 secreted polypeptide ligands. EGFRs are overexpressed in many solid tumors, including breast, pancreas, head-and-neck, prostate, ovarian, renal, colon, and non-small-cell lung cancer. Such overexpression produces strong stimulation of downstream signaling pathways, which induce cell growth, cell differentiation, cell cycle progression, angiogenesis, cell motility and blocking of apoptosis.The high expression and/or functional activation of EGFRs correlates with the pathogenesis and progression of several cancers, which make them attractive targets for both diagnosis and therapy. Several approaches have been developed to target these receptors and/or the EGFR modulated effects in cancer cells. Most approaches include the development of anti-EGFRs antibodies and/or small-molecule EGFR inhibitors. This review presents the state-of-the-art and future prospects of targeting EGFRs to treat breast cancer.

scholarly journals The Motile Breast Cancer Phenotype Roles of Proteoglycans/Glycosaminoglycans

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Dragana Nikitovic ◽  
Katerina Kouvidi ◽  
Kallirroi Voudouri ◽  
Aikaterini Berdiaki ◽  
Evgenia Karousou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Downstream Signaling ◽  
Insulin Growth Factor ◽  
Cancer Pathogenesis ◽  
Cellular Mediators ◽  
Epidermal Growth ◽  
Cancer Phenotype ◽  
Insulin Growth Factor Receptor

The consecutive stages of cancer growth and dissemination are obligatorily perpetrated through specific interactions of the tumor cells with their microenvironment. Importantly, cell-associated and tumor microenvironment glycosaminoglycans (GAGs)/proteoglycan (PG) content and distribution are markedly altered during tumor pathogenesis and progression. GAGs and PGs perform multiple functions in specific stages of the metastatic cascade due to their defined structure and ability to interact with both ligands and receptors regulating cancer pathogenesis. Thus, GAGs/PGs may modulate downstream signaling of key cellular mediators including insulin growth factor receptor (IGFR), epidermal growth factor receptor (EGFR), estrogen receptors (ERs), or Wnt members. In the present review we will focus on breast cancer motility in correlation with their GAG/PG content and critically discuss mechanisms involved. Furthermore, new approaches involving GAGs/PGs as potential prognostic/diagnostic markers or as therapeutic agents for cancer-related pathologies are being proposed.

Prognostic value of epidermal growth factor receptor (EGFR) family members in breast cancer.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e21079-e21079
Author(s):  
T. Badovinac Crnjevic ◽  
J. Jakic-Razumovic ◽  
D. Vrbanec ◽  
A. Juretic ◽  
S. Plestina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Prognostic Value ◽  
Family Members ◽  
Growth Factor Receptor ◽  
Epidermal Growth ◽  
Egfr Family

scholarly journals Efficacy of a CDK4/6 Inhibitor in a Patient with Breast Cancer and Liposarcoma: A Case Report and Review of the Literature

Breast Care ◽  
2018 ◽  
Vol 14 (5) ◽  
pp. 325-328
Author(s):  
Laura Loretan ◽  
Linda Eszter Moskovszky ◽  
Michael Kurrer ◽  
G. Ulrich Exner ◽  
Andreas Trojan
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Cell Cycle Progression ◽  
Therapeutic Potential ◽  
Growth Factor Receptor ◽  
Cycle Progression ◽  
Rb Pathway ◽  
Epidermal Growth ◽  
Well Differentiated

Background: The cyclin D/cyclin-dependent kinase (CDK)4/6 inhibitor of the CDK4 (INK4)/retinoblastoma (Rb) pathway plays a crucial role in cell cycle progression. Selective CDK4/6 inhibitors specifically target a variety of tumors, with the main focus on hormone receptor(HR)-positive and human epidermal growth factor receptor 2(HER2)-negative breast cancer (BC). Case Report: We report on the efficacy of neoadjuvant palbociclib and letrozole application in a patient suffering from invasive estrogen receptor (ER)+/HER2- BC and concurrent well-differentiated and dedifferentiated liposarcoma (WD-DDLPS) of the thigh. Clinical and histological workup upon surgery revealed significant regressive changes in both the liposarcoma and the BC. The 24-month follow-up shows no signs of disease. Conclusion: CDK4/6 inhibitors exhibit a high therapeutic potential, although reliable prognostic markers need to be identified.

scholarly journals Conserved roles for receptor tyrosine kinase extracellular regions in regulating receptor and pathway activity

2020 ◽  
Vol 477 (21) ◽  
pp. 4207-4220
Author(s):  
Monica Gonzalez-Magaldi ◽  
Jacqueline M. McCabe ◽  
Haley N. Cartwright ◽  
Ningze Sun ◽  
Daniel J. Leahy
Keyword(s):  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Receptor Phosphorylation ◽  
Surface Receptors ◽  
Animal Development ◽  
Downstream Signaling ◽  
Extracellular Region ◽  
Downstream Effectors ◽  
Epidermal Growth ◽  
Pathway Inhibition

Receptor Tyrosine Kinases (RTKs) comprise a diverse group of cell-surface receptors that mediate key signaling events during animal development and are frequently activated in cancer. We show here that deletion of the extracellular regions of 10 RTKs representing 7 RTK classes or their substitution with the dimeric immunoglobulin Fc region results in constitutive receptor phosphorylation but fails to result in phosphorylation of downstream signaling effectors Erk or Akt. Conversely, substitution of RTK extracellular regions with the extracellular region of the Epidermal Growth Factor Receptor (EGFR) results in increases in effector phosphorylation in response to EGF. These results indicate that the activation signal generated by the EGFR extracellular region is capable of activating at least seven different RTK classes. Failure of phosphorylated Fc-RTK chimeras or RTKs with deleted extracellular regions to stimulate phosphorylation of downstream effectors indicates that either dimerization and receptor phosphorylation per se are insufficient to activate signaling or constitutive dimerization leads to pathway inhibition.

scholarly journals Targeting of solid tumors and blood malignancies by antibody-based therapies — EGFR-pathway as an example

2006 ◽  
Vol 1 (2) ◽  
pp. 167-182 ◽  
Author(s):  
Krzysztof Krzemieniecki ◽  
Elzbieta Szpyt ◽  
Iran Rashedi ◽  
Katarzyna Gawron ◽  
Marek Los
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Solid Tumors ◽  
Tyrosine Kinases ◽  
Mapk Pathway ◽  
Growth Factor Receptor ◽  
Hematologic Malignancies ◽  
Mitogen Activated Protein Kinase ◽  
Epidermal Growth ◽  
Egfr Family

AbstractA well-coordinated interaction between extracellular signals and intracellular response forms the basis of life within multicellular organisms, with growth factors playing a crucial role in these interactions. Discoveries in recent years have shown that components of the Epidermal Growth Factor (EGF) signaling system have frequently been used by cancer cells to autonomously provide survival and proliferation signals. The main focus of this review is the ErbB epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases including ErbB1/EGFR, ErbB2/HER2/neu, ErbB3/HER3, and ErbB4/HER4 as therapeutic targets. Since the ErbB receptor family regulates cell proliferation through the Ras-mitogen-activated protein kinase (RAS/MAPK) pathway, and cell survival and transformation through the phosphatidylinositol 3-kinase (PI3K/AKT) pathway, pharmacological targeting of these pathways is also discussed. We will also address the clinical studies that have been conducted to evaluate antibody-based therapies mostly on solid tumors and hematologic malignancies.

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.

scholarly journals Genomic Profiling of Premenopausal HR+ and HER2– Metastatic Breast Cancer by Circulating Tumor DNA and Association of Genetic Alterations With Therapeutic Response to Endocrine Therapy and Ribociclib

2021 ◽  
pp. 1408-1420
Author(s):  
Aditya Bardia ◽  
Fei Su ◽  
Nadia Solovieff ◽  
Seock-Ah Im ◽  
Joohyuk Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Circulating Tumor Dna ◽  
Genetic Alterations ◽  
Wild Type ◽  
Hormone Receptor Positive ◽  
Epidermal Growth ◽  
Premenopausal Patients ◽  
Tumor Dna

PURPOSE This analysis evaluated the genomic landscape of premenopausal patients with hormone receptor–positive and human epidermal growth factor receptor 2–negative advanced breast cancer and the association of genetic alterations with response to ribociclib in the phase III MONALEESA-7 trial. METHODS Premenopausal patients were randomly assigned 1:1 to receive endocrine therapy plus ribociclib or placebo. Plasma collected at baseline was sequenced using targeted next-generation sequencing for approximately 600 relevant cancer genes. The association of circulating tumor DNA alterations with progression-free survival (PFS) was evaluated to identify biomarkers of response and resistance to ribociclib. RESULTS Baseline circulating tumor DNA was sequenced in 565 patients; 489 had evidence of ≥ 1 alteration. The most frequent alterations included PIK3CA (28%), TP53 (19%), CCND1 (10%), MYC (8%), GATA3 (8%), receptor tyrosine kinases (17%), and the Chr8p11.23 locus (12%). A treatment benefit of ribociclib was seen with wild-type (hazard ratio [HR] 0.45 [95% CI, 0.33 to 0.62]) and altered (HR 0.57 [95% CI, 0.36 to 0.9]) PIK3CA. Overall, patients with altered CCND1 had shorter PFS regardless of treatment, suggesting CCND1 as a potential prognostic biomarker. Benefit with ribociclib was seen in patients with altered (HR 0.21 [95% CI, 0.08 to 0.54]) or wild-type (HR 0.52 [95% CI, 0.39 to 0.68]) CCND1, but greater benefit was observed with altered, suggesting predictive potential of CCND1. Alterations in TP53, MYC, Chr8p11.23 locus, and receptor tyrosine kinases were associated with worse PFS, but ribociclib benefit was independent of alteration status. CONCLUSION In this study—to our knowledge, the first large study of premenopausal patients with hormone receptor–positive and human epidermal growth factor receptor 2–negative advanced breast cancer—multiple genomic alterations were associated with poor outcome. A PFS benefit of ribociclib was observed regardless of gene alteration status, although in this exploratory analysis, a magnitude of benefits varied by alteration.

scholarly journals Reciprocal Priming between RTKs within Recycling Endosomes Orchestrates Cellular Signaling Outputs

2021 ◽  
Author(s):  
Michael P. Smith ◽  
Harriet R. Ferguson ◽  
Jennifer Ferguson ◽  
Egor Zindy ◽  
Katarzyna M. Kowalczyk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Fibroblast Growth Factor Receptors ◽  
Recycling Endosomes ◽  
Phosphorylation Event ◽  
Epidermal Growth ◽  
Cellular Behaviour ◽  
Fine Tune

SUMMARYIntegration of signaling downstream from individual Receptor Tyrosine Kinases (RTKs) is crucial to fine tune cellular homeostasis during development and in pathological conditions, including breast cancer. However, how signalling integration is regulated and whether the endocytic fate of single receptors controls such signalling integration still remain poorly elucidated. Focusing on distinct Fibroblast Growth Factor Receptors (FGFRs) we generated a detailed picture of recycling-dependent FGF signalling in breast cancer cells by combining quantitative phosphoproteomics and targeted assays. We discovered reciprocal priming between FGFRs and Epidermal Growth Factor Receptor (EGFR) within recycling endosomes. FGFR recycling ligands induce EGFR phosphorylation on threonine 693. This phosphorylation event alters both FGFR and EGFR trafficking and primes FGFR-mediated cell cycle but not cell invasion. In turn, FGFR signaling primes EGF-mediated outputs. The discovery of reciprocal priming between distict families of RTKs within recycling endosomes will transform our understanding of signalling integration by pointing to recycling endosomes as crucial signalling hubs for orchestrating cellular behaviour. Therefore, targeting reciprocal priming rather than individual receptors may improve personalized therapies in breast and other cancers.

Sign in / Sign up

Export Citation Format

Share Document