Targeting signal transduction

Slides:

Advertisements

Similar presentations

BioSci 145A lecture 18 page 1 © copyright Bruce Blumberg All rights reserved BioSci 145A Lecture 18 - Oncogenes and Cancer Topics we will cover today.

Advertisements

 Regulation of Cell Number and Cancer Cells Special Limited Edition Packet Tuesday, November 10,

Overview of Targeted Therapy Mechanisms November 11, 2011 Targeted Therapies and Biological Therapies SIG.

Negative regulation of cell cycle by intracellular signals Checkpoint p53 detects DNA damage & activates p21 p21 inhibits cdk2-cyclinA Intracellular Regulation.

EUKARYOTIC CELL SIGNALING VII Abnormal Signaling in Cancer Signaling to p53 Dr. Ke Shuai Office: 9-240M Factor Tel: X69168

Cell-cycle checkpoint activation downstream of ATM and ATR

THE GENETIC BASIS OF CANCER

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

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.

Cell Signaling Pathways – A Case Study Approach

Combinatorial interactions of cyclins and cyclin-dependent kinases (cdks) during the cell cycle. Progression from G0 through the restriction point in G1.

An applied electric field induces polarized activation of PI3 kinase

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

Genetic instability in epithelial tissues compared to stromal tissues

Methods for site-directed mutagenesis

Angiogenic switch and progression during tumor development

Advances in Molecular Biology of Lung Disease

Figure 1. Resistance mechanism against first generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). (A) Mutations in the EGFR.

Structures of antiestrogens and aromatase inhibitors

Gatekeeper, caretaker, and landscaper mutations

Integration of cell death responses

Targeting the DNA Damage Response in Cancer

Activation of Oncogenic Pathways in Idiopathic Pulmonary Fibrosis

Figure 2 Crosstalk between TGF-β/Smad and other pathways in tissue fibrosis Figure 2 | Crosstalk between TGF-β/Smad and other pathways in tissue fibrosis.

Sustaining Proliferative Signaling and Evading Growth Suppressors

Juvenile Myelomonocytic Leukemia

Miriam Marqués, Francisco X. Real European Urology

Daniel Morgensztern, MD, Meghan J. Campo, MD, Suzanne E

Urokinase-induced smooth muscle cell responses require distinct signaling pathways: A role for the epidermal growth factor receptor Suzanne M. Nicholl,

Extracellular Regulation of Apoptosis

Figure 1 A schematic representation of the HER2 signalling pathway

Figure 2 Oestrogen receptor signalling pathways

Nat. Rev. Urol. doi: /nrurol

Nat. Rev. Nephrol. doi: /nrneph

Targeted Therapies in Melanoma: Translational Research at Its Finest

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

Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro

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

Cancer and the Cell Cycle

PTEN Enters the Nuclear Age

Figure 1 The insulin signalling pathway

Keratinocyte Apoptosis in Epidermal Development and Disease

Inhibition of mammalian target of rapamycin: Two goals with one shot?

Melanoma: New Insights and New Therapies

Nat. Rev. Urol. doi: /nrurol

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

Vascular Endothelial Growth Factor (VEGF) Pathway

Olga C. J. Schuurbiers, MD, Johannes H. A. M

Detection rate for EGFR mutations in cfDNA.

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

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

The RAS/MAPK Axis Gets Stressed Out

M.B.Ch.B, MSC, PhD, DCH (UK), MRCPCH

Figure 4 Bile-acid-induced TGR5 signalling pathways in macrophages

Summary of this study. Summary of this study. Cysteinyl-leukotrienes (cys-LTs) stimulate mitogenesis of bronchial fibroblasts only in the presence of RTK.

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

Platelet-derived growth factor (PDGF) signalling pathway.

Jinhua Tang, Na Liu, Shougang Zhuang Kidney International

The RAS-MEK-ERK pathway represents a chain of protein signalling pathway that responds to a mitogen binding to a cell surface receptor. The RAS-MEK-ERK.

The mitogen-activated protein kinase (MAPK) pathway showing mutations identified in pulmonary Langerhans cell histiocytosis (PLCH). The mitogen-activated.

Mutant BRAF Melanomas—Dependence and Resistance

Schematic representation of signaling pathways modulated by PKD1 in cancer. Schematic representation of signaling pathways modulated by PKD1 in cancer.

Model for the regulation of HIPK2 activity and p53 phosphorylations by the ATM pathway. Model for the regulation of HIPK2 activity and p53 phosphorylations.

Signalling pathways and involved entities that are unravelling experimental therapeutic targets for TNBC. Depicted molecular landscape of TNBC confers.

Phases of the Cell Cycle

Phases of the Cell Cycle

Tenets of PTEN Tumor Suppression

Successful targeting of ErbB2 receptors—is PTEN the key?

Overview of molecular JAK signaling.

HER2 and PI3K-targeted therapies result in FOXO3a-mediated feedback upregulation of HER3 and IGF1R and provide an escape from PI3K pathway inhibition.

Presentation transcript:

Targeting signal transduction Targeting signal transduction. Growth factor receptor activation by mutation or overexpression, or mutations in oncogenes (such as RAS) or tumor suppressor genes (such as PTEN) can lead to signaling through the phophatidylinositol-3 kinase (PI3K)-AKT, mitogen-activated protein kinase (MAPK)-extracellular signal regulated kinase (ERK), nuclear factor-κB (NF-κB), and transforming growth factor-β (TGFβ) pathways. Such signaling can affect radiosensitivity by decreasing apoptosis (left) or increasing DNA repair (right). AKT, MAPK, and NF-κB signaling can all lead to phosphorylation and inactivation of proapoptotic proteins or activation of antiapoptotic proteins. Altering apoptosis does not always lead to changes in clonogenic cell survival (dashed arrow with question mark). Activation of the AKT and MAPK pathways leads to the activation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), a central protein in DSB repair by NHEJ. Direct inhibition of DNA repair may also lead to radiosensitization by targeting the ATM and DNA-PKcs kinases or PARP proteins. DNA-PKcs can also be activated by the receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR) after it is translocated to the nucleus. There is a strong correlation between DNA repair capacity, particularly for DSBs, and radiosensitivity. Ionizing radiation can also activate the PI3K, MAPK, and NF-κB pathways. Inhibition of signaling pathways following irradiation can therefore reverse (Begg et al, 2011) tumor cell radioresistance. Some inhibitors have also been shown to affect tumor vasculature, leading to improved perfusion and reduced hypoxia (see also Chap. 16, Sec. 16.2.5). Asterisk indicates activation. (Taken from Begg et al, 2011.) Source: Molecular and Cellular Basis of Radiotherapy, The Basic Science of Oncology, 5e Citation: Tannock IF, Hill RP, Bristow RG, Harrington L. The Basic Science of Oncology, 5e; 2016 Available at: http://hemonc.mhmedical.com/DownloadImage.aspx?image=/data/Books/1791/tanbas5_Ach15_f017.png&sec=124304841&BookID=1791&ChapterSecID=124304756&imagename= Accessed: January 01, 2018 Copyright © 2018 McGraw-Hill Education. All rights reserved