Yan Feng, MD, Praveena S. Thiagarajan, PhD, Patrick C. Ma, MD

Slides:

Advertisements

Similar presentations

Lecture 23 Signal Transduction 2

Advertisements

Chap. 16 Signaling Pathways That Control Gene Expression

Signal Transduction II Transduction Proteins & Second Messengers.

Gene Transcription G0G0 G1G1 Priming S G2G2 M Cell Cell Cycle Growth Factors + Growth Factors & Cell Cycle Receptors.

Specialized signaling pathways 1: RTK associated pathways

Integrin-EGFR Cross-Activation Elizabeth Brooks Department of Chemical Engineering University of Massachusetts, Amherst Peyton Lab Group Meeting December.

Date of download: 7/5/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved. Insulin signaling pathways. The insulin signaling pathways provide.

Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non- small cell lung cancer: Focus on epidermal growth factor receptor.

Lung Cancer Tumour Markers

Model for regulation of the Ras p21 product and for the GTPase-activating protein (GAP) as a downstream effector and regulator of ras activity. Ras is.

Silvestri Gerard A. , MD, FCCP, Rivera M. Patricia , MD, FCCP CHEST

Advances in Molecular Biology of Lung Disease

Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical.

Intercellular Communication

Akihito Muto, MD, PhD, Tamara N. Fitzgerald, MD, PhD, Jose M

Activation of Oncogenic Pathways in Idiopathic Pulmonary Fibrosis

Molecular regulation of mast cell activation

Sustaining Proliferative Signaling and Evading Growth Suppressors

Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies Nima Rezaei, MD, PhD, Mona Hedayat, MD,

Miriam Marqués, Francisco X. Real European Urology

Targeting MET in Lung Cancer: Will Expectations Finally Be MET?

cMET Exon 14 Skipping: From the Structure to the Clinic

Figure 1 A schematic representation of the HER2 signalling pathway

Signal Transduction Through the Epidermal Growth Factor Receptor

Signaling molecules as therapeutic targets in allergic diseases

Targeting ROS1 with Anaplastic Lymphoma Kinase Inhibitors: A Promising Therapeutic Strategy for a Newly Defined Molecular Subset of Non–Small-Cell Lung.

Figure 2 HGF/c-MET signalling pathway

Mechanisms of mast cell signaling in anaphylaxis

Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer Roberto Ferrara, MD, Nathalie Auger, MD, Edouard Auclin,

Axl Receptor Axis: A New Therapeutic Target in Lung Cancer

Molecular regulation of mast cell activation

BDNF and insulin signaling pathways activated by phytochemicals.

Nat. Rev. Nephrol. doi: /nrneph

Bryan A. Whitson, MD, Blake A

Development of PI3K/AKT/mTOR Pathway Inhibitors and Their Application in Personalized Therapy for Non–Small-Cell Lung Cancer Vassiliki Papadimitrakopoulou,

Bhagelu Ram Achyut, Li Yang Gastroenterology

Schematic view of Trk receptors signalling, showing the three major pathways involved in cell differentiation and survival. Schematic view of Trk receptors.

EGFR T790M Mutation: A Double Role in Lung Cancer Cell Survival?

Identification of TOR Signaling Complexes

Inflammation, Epithelial to Mesenchymal Transition, and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance Kostyantyn Krysan, PhD,

Durable Response to Afatinib in Lung Adenocarcinoma Harboring NRG1 Gene Fusions Nathan D. Gay, MD, Ying Wang, MD, Carol Beadling, PhD, Andrea Warrick,

Shannon Otsuka, BSc, Gwyn Bebb, BMBCh, PhD, FRCPC

BRAF Alterations as Therapeutic Targets in Non–Small-Cell Lung Cancer

Vascular Endothelial Growth Factor (VEGF) Pathway

FGFR Signaling as a Target for Lung Cancer Therapy

The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing Marieke Hylebos, MSc, Guy Van Camp, PhD, Jan P van.

Acquired EGFR Mutation as the Potential Resistance Driver to Crizotinib in a MET- Mutated Tumor Marc-Antoine Benderra, MD, Sandrine Aspeslagh, PhD, Sophie.

Met as a therapeutic target in HCC: Facts and hopes

Volume 18, Issue 1, Pages (July 2013)

Live Longer sans the AT1A Receptor

Volume 73, Issue 1, Pages 5-7 (January 2008)

Vascular Endothelial Growth Factor and Epidermal Growth Factor Signaling Pathways as Therapeutic Targets for Colorectal Cancer Thomas Winder, Heinz–Josef.

Primary Double-Strike Therapy for Cancers to Overcome EGFR Kinase Inhibitor Resistance: Proposal from the Bench Kenichi Suda, MD, PhD, Paul A. Bunn,

Signal Transduction Through the Epidermal Growth Factor Receptor

AKT/PKB Signaling: Navigating Downstream

SRC and STAT Pathways Journal of Thoracic Oncology

Signalling links in the liver: Knitting SOCS with fat and inflammation

SOCS Proteins, Regulators of Intracellular Signaling

Benjamin Solomon, MBBS, PhD, Richard B. Pearson, PhD

Acetylcholine Receptor Pathway and Lung Cancer

Simon Ekman, MD, PhD, Murry W. Wynes, PhD, Fred R. Hirsch, MD, PhD

Platelet-derived growth factor (PDGF) signalling pathway.

GPC5 Gene and Its Related Pathways in Lung Cancer

Molecular Characterization of Acquired Resistance to the BRAF Inhibitor Dabrafenib in a Patient with BRAF-Mutant Non–Small-Cell Lung Cancer Charles M.

The new kid on the block(ade) of the IGF-1 receptor

Figure 2 Signalling downstream of the IL-6 receptor

Friends with Benefits: Microenvironmental NRG1β and HGF Mediate HER2-Targeted Resistance in L-HER2+ and HER2E Breast Cancer Sarah B. Crist, Cyrus M.

Notch signaling from tumor cells: A new mechanism of angiogenesis

Brief Review – Growth Factors and Receptors

Successful targeting of ErbB2 receptors—is PTEN the key?

Presentation transcript:

MET Signaling: Novel Targeted Inhibition and Its Clinical Development in Lung Cancer Yan Feng, MD, Praveena S. Thiagarajan, PhD, Patrick C. Ma, MD Journal of Thoracic Oncology Volume 7, Issue 2, Pages 459-467 (February 2012) DOI: 10.1097/JTO.0b013e3182417e44 Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 MET receptor signaling and strategies of therapeutic inhibition in lung cancer. The natural ligand for MET is hepatocyte growth factor (HGF), also called scatter factor (SF). Aberrant HGF stimulation of MET in human cancer can occur by aberrant autocrine (intratumoral), paracrine (mircoenvironmental), or endocrine (circulatory) loop signal activation. Upon HGF binding to the Sema domain, MET dimerizes leading to autophosphorylation of intracellular tyrosine residues Y1230/Y1234/Y1235 followed by the phosphorylation of Y1349 and Y1356 near the carboxyl terminal portion. MET activation results in the recruitment and activation of downstream adaptor proteins and kinase targets resulting in a multitude of effects such as increased cell proliferation, cell cycle progression, scattering, motility, survival, extracellular matrix remodeling, and changes in metabolism. Thus, MET signaling contributes to tumor growth, scattering, motility, invasiveness, and metastasis, thereby playing important roles in mediating tumor addiction/dependence and tumor expedience. Therapeutic intervention strategies to block and inhibit MET receptor oncogenic signaling cascade include blocking ligand-receptor interaction, preventing receptor dimerization, blocking MET kinase intrinsic activity, and inhibiting specific downstream signal transducers. PI3K, phosphatidylinositol 3-kinase; GRB2, growth factor receptor-bound protein 2; GAB1, Grb2-associated adaptor protein1; STAT 3/5, signal transducer and activator of transcription 3/5; mTOR, mammalian target of rapamycin; SOS, son of sevenless; SHP2, SRC homology protein tyrosine phosphatase 2; SHC, SRC homology domain; PLC-γ, phospholipase c-γ; RAS, rat sarcoma oncogene homolog; MAPK, mitogen-activated protein kinase; RAC1, Ras-related C3 botulinum toxin substrate 1; RHO, Ras homologos; PAX, paxillin; FAK, focal adhesion kinase. Journal of Thoracic Oncology 2012 7, 459-467DOI: (10.1097/JTO.0b013e3182417e44) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions