Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways.
Ping Wee,Zhixiang Wang +1 more
TLDR
The molecular mechanisms that regulate EGFR signal transduction are reviewed, including the EGFR structure and its mutations, ligand binding and EGFR dimerization, as well as the signaling pathways that lead to G1 cell cycle progression.Abstract:
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation These EGFR aberrations over-activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways These pathways then activate many biological outputs that are beneficial to cancer cell proliferation, including their chronic initiation and progression through the cell cycle Here, we review the molecular mechanisms that regulate EGFR signal transduction, including the EGFR structure and its mutations, ligand binding and EGFR dimerization, as well as the signaling pathways that lead to G1 cell cycle progression We focus on the induction of CYCLIN D expression, CDK4/6 activation, and the repression of cyclin-dependent kinase inhibitor proteins (CDKi) by EGFR signaling pathways We also discuss the successes and challenges of EGFR-targeted therapies, and the potential for their use in combination with CDK4/6 inhibitorsread more
Citations
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Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis.
Yixiao Feng,Yixiao Feng,Mia Spezia,Shifeng Huang,Shifeng Huang,Chengfu Yuan,Chengfu Yuan,Zongyue Zeng,Zongyue Zeng,Linghuan Zhang,Linghuan Zhang,Xiaojuan Ji,Xiaojuan Ji,Wei Liu,Wei Liu,Bo Huang,Bo Huang,Bo Huang,Wenping Luo,Wenping Luo,Bo Liu,Bo Liu,Yan Lei,Yan Lei,Scott Du,Akhila Vuppalapati,Hue H. Luu,Rex C. Haydon,Tong-Chuan He,Guosheng Ren +29 more
TL;DR: Emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer, especially for triple-negative breast cancer.
Journal ArticleDOI
Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer.
TL;DR: The molecular characteristics of the main lung cancer subtypes are discussed and the current guidelines and novel targeted therapies, including checkpoint immunotherapy are discussed.
Journal ArticleDOI
EGFR heterogeneity and implications for therapeutic intervention in glioblastoma
Eskil Eskilsson,Gro V. Røsland,Gergely Solecki,Qianghu Wang,Patrick N. Harter,Grazia Graziani,Roel G.W. Verhaak,Frank Winkler,Rolf Bjerkvig,Hrvoje Miletic,Hrvoje Miletic +10 more
TL;DR: The clonal and functional heterogeneity of EGFRs in GBM development is discussed, the potential of EG FRs as therapeutic targets are critically reassessed, and treatment strategies targeting EGFR haveThus far failed in clinical trials.
Journal ArticleDOI
Signaling pathways involved in colorectal cancer progression.
Zahra Koveitypour,Farnoush Panahi,Mehrdad Vakilian,Mehrdad Vakilian,Maryam Peymani,Maryam Peymani,Farzad Seyed Forootan,Farzad Seyed Forootan,Mohammad Hossein Nasr Esfahani,Kamran Ghaedi,Kamran Ghaedi +10 more
TL;DR: This review will focus on the mitogen-activated protein kinase (MAPK) cascades downstream of the epidermal growth factor receptor (EGFR), Notch, PI3K/AKT pathway, transforming growth factor-β (TGF-β), and Wnt signaling pathways.
Journal ArticleDOI
Brain Tumor Microenvironment and Host State: Implications for Immunotherapy
TL;DR: Lowering the barrier of immunosuppression by targeting the genetically stable tumor stroma presents opportunities to treat the tumor in a way that circumvents the complications of targeting a constantly mutating tumor with tumor antigen–directed therapies.
References
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Journal ArticleDOI
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Journal ArticleDOI
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene
Dennis J. Slamon,Gary M. Clark,Steven G. Wong,Wendy J. Levin,Axel Ullrich,William L. McGuire +5 more
TL;DR: Amplification of the HER-2/neu gene was a significant predictor of both overall survival and time to relapse in patients with breast cancer, and had greater prognostic value than most currently used prognostic factors in lymph node-positive disease.
Journal ArticleDOI
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
Thomas J. Lynch,Daphne W. Bell,Raffaella Sordella,Sarada Gurubhagavatula,Ross A. Okimoto,Brian W. Brannigan,Patricia L. Harris,Sara M. Haserlat,Jeffrey G. Supko,Frank G. Haluska,David N. Louis,David C. Christiani,Jeff Settleman,Daniel A. Haber +13 more
TL;DR: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, and these mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor.
Journal ArticleDOI
Mutations of the BRAF gene in human cancer
Helen Davies,Graham R. Bignell,Charles Cox,Philip J. Stephens,Sarah Edkins,S. M. Clegg,Jon W. Teague,Hayley Woffendin,Mathew J. Garnett,William Bottomley,Neil Davis,Ed Dicks,Rebecca Ewing,Yvonne Floyd,Kristian Gray,S. Hall,Rachel Hawes,Jaime Hughes,Vivian Kosmidou,Andrew Menzies,Catherine Mould,Adrian Parker,Claire Stevens,Stephen Watt,Steven Hooper,Rebecca Wilson,Hiran Jayatilake,Barry A. Gusterson,Colin Cooper,Janet Shipley,Darren Hargrave,Kathy Pritchard-Jones,Norman J. Maitland,Georgia Chenevix-Trench,Gregory J. Riggins,Darell D. Bigner,Giuseppe Palmieri,Antonio Cossu,Adrienne M. Flanagan,Andrew G. Nicholson,Judy W. C. Ho,Suet Yi Leung,Siu Tsan Yuen,Barbara L. Weber,Hilliard F. Seigler,Timothy L. Darrow,Hugh Paterson,Richard Marais,Christopher J. Marshall,Richard Wooster,Michael R. Stratton,P. Andrew Futreal +51 more
TL;DR: BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%.
Journal ArticleDOI
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
J. Guillermo Paez,Pasi A. Jänne,Pasi A. Jänne,Jeffrey C. Lee,Sean Tracy,Heidi Greulich,Heidi Greulich,Stacey Gabriel,Paula Herman,Frederic J. Kaye,Neal I. Lindeman,Titus J. Boggon,Katsuhiko Naoki,Hidefumini Sasaki,Yoshitaka Fujii,Michael J. Eck,William R. Sellers,William R. Sellers,William R. Sellers,Bruce E. Johnson,Bruce E. Johnson,Matthew Meyerson,Matthew Meyerson +22 more
TL;DR: Results suggest that EGFR mutations may predict sensitivity to gefitinib, and treatment with the EGFR kinase inhibitor gefitsinib causes tumor regression in some patients with NSCLC, more frequently in Japan.