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

Slides:



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

Inducible EGFR T790M-Mediated Gefitinib Resistance in Non-small Cell Lung Cancer Cells Does Not Modulate Sensitivity to PI103 Provoked Autophagy  Flavia.
Frances A Shepherd, MD, Rafael Rosell, MD  Journal of Thoracic Oncology 
Silvestri Gerard A. , MD, FCCP, Rivera M. Patricia , MD, FCCP  CHEST 
Advances in Molecular Biology of Lung Disease
Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non– Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor.
Peyman Hadji, Robert Coleman, Michael Gnant 
Targeting signal transduction
Phase II Study of Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), and Celecoxib, a Cyclooxygenase-2 (COX-2) Inhibitor,
Epidermal Growth Factor Receptor-Related Tumor Markers and Clinical Outcomes with Erlotinib in Non-small Cell Lung Cancer: An Analysis of Patients from.
Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in.
Treatment of Glioma in the 21st Century: An Exciting Decade of Postsurgical Treatment Advances in the Molecular Era  Joon H. Uhm, MD, Alyx B. Porter,
Malignant Pleural Mesothelioma Harboring Both G719C and S768I Mutations of EGFR Successfully Treated with Afatinib  Nobukazu Agatsuma, MD  Journal of.
Malignant Pleural Mesothelioma Harboring Both G719C and S768I Mutations of EGFR Successfully Treated with Afatinib  Nobukazu Agatsuma, MD  Journal of.
Rash in a Patient Treated with Pemetrexed for Relapsed Non-small Cell Lung Cancer  Isabelle Declercq, MD, Yolande Lievens, MD, PhD, Eric Verbeken, MD,
c-Kit as a Novel Potential Therapeutic Target in Colorectal Cancer
Volume 56, Issue 3, Pages (March 2012)
The CTC-Chip: An Exciting New Tool to Detect Circulating Tumor Cells in Lung Cancer Patients  Lecia V. Sequist, MD, MPH, Sunitha Nagrath, PhD, Mehmet.
Personalizing Therapy for Colorectal Cancer
Targeting ROS1 with Anaplastic Lymphoma Kinase Inhibitors: A Promising Therapeutic Strategy for a Newly Defined Molecular Subset of Non–Small-Cell Lung.
Clinical and Translational Implications of RET Rearrangements in Non–Small Cell Lung Cancer  Roberto Ferrara, MD, Nathalie Auger, MD, Edouard Auclin,
Personalizing Therapy for Colorectal Cancer
GLP-1–Based Therapies: The Dilemma of Uncertainty
Association of Epidermal Growth Factor Receptor Activating Mutations with Low ERCC1 Gene Expression in Non-small Cell Lung Cancer  David R. Gandara, MD,
Development of PI3K/AKT/mTOR Pathway Inhibitors and Their Application in Personalized Therapy for Non–Small-Cell Lung Cancer  Vassiliki Papadimitrakopoulou,
EGFR T790M Mutation: A Double Role in Lung Cancer Cell Survival?
Inducible EGFR T790M-Mediated Gefitinib Resistance in Non-small Cell Lung Cancer Cells Does Not Modulate Sensitivity to PI103 Provoked Autophagy  Flavia.
Combining the Multitargeted Tyrosine Kinase Inhibitor Vandetanib with the Antiestrogen Fulvestrant Enhances Its Antitumor Effect in Non-small Cell Lung.
Bob T. Li, M. B. B. S. , MPH, Dara S. Ross, MD, Dara L
Glucose Metabolism in NSCLC Is Histology-Specific and Diverges the Prognostic Potential of 18FDG-PET for Adenocarcinoma and Squamous Cell Carcinoma  Olga.
Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in.
Estrogen Receptor (ER) and Epidermal Growth Factor Receptor (EGFR) as Targets for Dual Lung Cancer Therapy: Not Just a Case?  Monica Giovannini, MD, Carmen.
PTPRF Expression as a Potential Prognostic/Predictive Marker for Treatment with Erlotinib in Non-Small-Cell Lung Cancer  Denis Soulières, MD, Fred R.
Shannon Otsuka, BSc, Gwyn Bebb, BMBCh, PhD, FRCPC 
Comprehensive Hybrid Capture–Based Next-Generation Sequencing Identifies a Double ALK Gene Fusion in a Patient Previously Identified to Be False-Negative.
BRAF Alterations as Therapeutic Targets in Non–Small-Cell Lung Cancer
ALK and NRG1 Fusions Coexist in a Patient with Signet Ring Cell Lung Adenocarcinoma  Lucia Anna Muscarella, PhD, Domenico Trombetta, PhD, Federico Pio.
Vascular Endothelial Growth Factor (VEGF) Pathway
Association of Phosphorylated Epidermal Growth Factor Receptor with Survival in Patients with Locally Advanced Non-small Cell Lung Cancer Treated with.
FGFR Signaling as a Target for Lung Cancer Therapy
Combined Use of ALK Immunohistochemistry and FISH for Optimal Detection of ALK- Rearranged Lung Adenocarcinomas  Lynette M. Sholl, MD, Stanislawa Weremowicz,
Lovastatin Sensitizes Lung Cancer Cells to Ionizing Radiation: Modulation of Molecular Pathways of Radioresistance and Tumor Suppression  Toran Sanli,
Deregulation of p27 and Cyclin D1/D3 Control Over Mitosis Is Associated with Unfavorable Prognosis in Non-small Cell Lung Cancer, as Determined in 405.
Potential Role of Platelet-Derived Growth Factor Receptor Inhibition Using Imatinib in Combination with Docetaxel in the Treatment of Recurrent Non-small.
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.
Spheroid Culture of Primary Lung Cancer Cells with Neuregulin 1/HER3 Pathway Activation  Hiroko Endo, BPHRM, Jiro Okami, MD, PhD, Hiroaki Okuyama, MD,
Volume 139, Issue 5, (November 2009)
Primary Double-Strike Therapy for Cancers to Overcome EGFR Kinase Inhibitor Resistance: Proposal from the Bench  Kenichi Suda, MD, PhD, Paul A. Bunn,
Clinical Significance of Epidermal Growth Factor Receptors in Non-small Cell Lung Cancer and a Prognostic Role for HER2 Gene Copy Number in Female Patients 
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non–Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis  Bin-Chi Liao,
Do Complex Mutations of the Epidermal Growth Factor Receptor Gene Reflect Intratumoral Heterogeneity?  Akito Hata, MD, Shiro Fujita, MD, PhD, Reiko Kaji,
The Prognostic Value of Chromosome 7 Polysomy in Non-small Cell Lung Cancer Patients Treated with Gefitinib  Lela E. Buckingham, PhD, John S. Coon, MD,
A Pilot Study of Preoperative Gefitinib for Early-Stage Lung Cancer to Assess Intratumor Drug Concentration and Pathways Mediating Primary Resistance 
Erratum Journal of Thoracic Oncology
A Different Method in Diagnosis of Multiple Primary Lung Cancer
Arnaud Uguen, MD, PhD  Journal of Thoracic Oncology 
SRC and STAT Pathways Journal of Thoracic Oncology
Novel Epidermal Growth Factor Receptor Mutation-Specific Antibodies for Non-small Cell Lung Cancer: Immunohistochemistry as a Possible Screening Method.
Yan Feng, MD, Praveena S. Thiagarajan, PhD, Patrick C. Ma, MD 
ALK Translocation in Non-small Cell Lung Cancer with Adenocarcinoma and Squamous Cell Carcinoma Markers  Samuel J. Klempner, MD, David W. Cohen, MD, Daniel.
Comparison of Clinical Outcomes Following Gefitinib and Erlotinib Treatment in Non– Small-Cell Lung Cancer Patients Harboring an Epidermal Growth Factor.
Osimertinib for Epidermal Growth Factor Receptor Mutation–Positive Lung Adenocarcinoma That Transformed to T790M-Positive Squamous Cell Carcinoma  Naoyuki.
EGFR delE709_T710insD: A Rare but Potentially EGFR Inhibitor Responsive Mutation in Non–Small-Cell Lung Cancer  Allison Ackerman, MD, Michael A. Goldstein,
Benjamin Solomon, MBBS, PhD, Richard B. Pearson, PhD 
Immunohistochemistry is a Reliable Screening Tool for Identification of ALK Rearrangement in Non–Small-Cell Lung Carcinoma and is Antibody Dependent 
Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non– Small Cell Lung Cancer  Emily Castellanos, MD, Emily Feld, MD, Leora.
Simon Ekman, MD, PhD, Murry W. Wynes, PhD, Fred R. Hirsch, MD, PhD 
Genetic Changes in Squamous Cell Lung Cancer: A Review
Waxing and Waning of MET Amplification in EGFR-Mutated NSCLC in Response to the Presence and Absence of Erlotinib Selection Pressure  Joel P. Womack,
Presentation transcript:

The PI3-K/AKT-Pathway and Radiation Resistance Mechanisms in Non-small Cell Lung Cancer  Olga C.J. Schuurbiers, MD, Johannes H.A.M. Kaanders, MD, PhD, Henricus F.M. van der Heijden, MD, PhD, Richard P.N. Dekhuijzen, MD, PhD, Wim J.G. Oyen, MD, PhD, Johan Bussink, MD, PhD  Journal of Thoracic Oncology  Volume 4, Issue 6, Pages 761-767 (June 2009) DOI: 10.1097/JTO.0b013e3181a1084f Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 The phosphatidylinositol-3-kinase/protein-kinase B (PI3-K/AKT) pathway and other major downstream targets of the ErbB tyrosine-kinase receptor. TK, tyrosine kinase; PI3-K, phosphatidylinositol-3-kinase; AKT, protein-kinase B; PTEN, phosphatase and TENsin homologue; mTOR, mammalian target of rapamycine; MAPK, mitogen-activated protein kinase. Journal of Thoracic Oncology 2009 4, 761-767DOI: (10.1097/JTO.0b013e3181a1084f) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 A mouse adenocarcinoma treated with radiotherapy. A, control; B, 0.5 Gy; C, 1 Gy; D, 2 Gy. Mouse adenocarcinoma treated with radiotherapy. Hypoxic areas are green (pimidazole). DNA double strand breaks are visualized after immunohistochemical staining of γH2AX. Nuclei are blue (Hoechst 33342). A dose dependent increase in γH2AX-foci is observed with more double strand breaks in normoxic tumor areas, indicating increased radioresistance of hypoxic tumor cells. Journal of Thoracic Oncology 2009 4, 761-767DOI: (10.1097/JTO.0b013e3181a1084f) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Fluorescent microscopic images of an undifferentiated non-small cell lung tumor (fine needle biopsy). (A) extensive areas of the endogenous hypoxia-related marker CA-9 (red/purple) indicates the presence of potentially radioresistant hypoxic tumor cells. Tumor nuclei are blue (Hoechst 33342), magnification ×20. (B) phosphorylated, activated, AKT-expression (pAKT, green), and EGFR-expression (red) relative to tumor nuclei (blue). Mismatch of epidermal growth factor receptor (EGFR) and activated protein kinase B (pAKT) illustrating the fact that the PI3-K/AKT-signaling pathway can be activated independent of the EGFR (magnification ×40). Journal of Thoracic Oncology 2009 4, 761-767DOI: (10.1097/JTO.0b013e3181a1084f) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions