Folylpoly-Glutamate Synthetase Expression Is Associated with Tumor Response and Outcome from Pemetrexed-Based Chemotherapy in Malignant Pleural Mesothelioma 

Slides:



Advertisements
Similar presentations
Efficacy and Safety of Pemetrexed Maintenance Therapy versus Best Supportive Care in Patients from East Asia with Advanced, Nonsquamous Non-small Cell.
Advertisements

Irinotecan, Carboplatin, and Imatinib in Untreated Extensive-Stage Small-Cell Lung Cancer: A Phase II Trial of the Minnie Pearl Cancer Research Network 
Epidermal Growth Factor Receptor-Related Tumor Markers and Clinical Outcomes with Erlotinib in Non-small Cell Lung Cancer: An Analysis of Patients from.
Liver Metastasis Is Associated with Poor Progression-Free Survival in Patients with Non–Small Cell Lung Cancer Treated with Nivolumab  Tomoko Funazo,
Laurence J. Egan, M.B., William J. Sandborn, M.D 
Perioperative versus Preoperative Chemotherapy with Surgery in Patients with Resectable Squamous Cell Carcinoma of Esophagus  Yang Zhao, MD, ZhiJun Dai,
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.
Maintenance Sunitinib following Initial Platinum-Based Combination Chemotherapy in Advanced-Stage IIIB/IV Non–Small Cell Lung Cancer: A Randomized, Double-Blind,
Phase II Trial with Carboplatin and Bendamustine in Patients with Extensive Stage Small-Cell Lung Cancer  Wolf Köster, MD, Andrea Heider, MD, Norbert.
Irinotecan, Carboplatin, and Imatinib in Untreated Extensive-Stage Small-Cell Lung Cancer: A Phase II Trial of the Minnie Pearl Cancer Research Network 
Genetic Determinants of Pemetrexed Responsiveness and Nonresponsiveness in Non- small Cell Lung Cancer Cells  Ming-Fang Wu, MD, PhD, Yi-Min Hsiao, PhD,
Prognostic Significance of TAZ Expression in Resected Non-Small Cell Lung Cancer  Mian Xie, MD, PhD, Li Zhang, MD, Chao-Sheng He, MD, Jin-Hui Hou, MD,
Figure 1 Pharmacodynamics of methotrexate in RA
Sunny Guin, PhD, Yuanbin Ru, PhD, Murry W
Nat. Rev. Rheumatol. doi: /nrrheum
High Prevalence of Concomitant Oncogene Mutations in Prospectively Identified Patients with ROS1-Positive Metastatic Lung Cancer  Marcel Wiesweg, MD,
Phase I Trial of Cediranib in Combination with Cisplatin and Pemetrexed in Chemonaive Patients with Unresectable Malignant Pleural Mesothelioma (SWOG.
Incidence and Survival of Malignant Pleural Mesothelioma in Norway: A Population- Based Study of 1686 Cases  Åslaug Helland, MD, PhD, Steinar Solberg,
Nicolas Girard, MD, Julie Teruya-Feldstein, MD, Eden C
Three-Year Follow-Up of a Randomized Phase II Trial on Refinement of Early-Stage NSCLC Adjuvant Chemotherapy with Cisplatin and Pemetrexed versus Cisplatin.
Complement and Correction for Meta-Analysis of Patients with Extensive-Stage Small Cell Lung Cancer Managed with Irinotecan/Cisplatin versus Etoposide/Cisplatin.
Low ERCC1 Expression in Malignant Pleural Mesotheliomas Treated with Cisplatin and Vinorelbine Predicts Prolonged Progression-Free Survival  Zarah Glad.
PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer  Hui Yu, MD, PhD, Cory Batenchuk, PhD,
Gemcitabine and Irinotecan for Patients with Untreated Extensive Stage Small Cell Lung Cancer: SWOG 0119  Wallace Akerley, MD, Jason McCoy, MS, Paul J.
Loss of Phosphatase and Tensin Homolog Protein Expression Is an Independent Poor Prognostic Marker in Lung Adenocarcinoma  Naoki Yanagawa, MD, PhD, Charles.
Glucocorticoid Receptor Status Is a Principal Determinant of Variability in the Sensitivity of Non–Small-Cell Lung Cancer Cells to Pemetrexed  Mugdha.
PTPRF Expression as a Potential Prognostic/Predictive Marker for Treatment with Erlotinib in Non-Small-Cell Lung Cancer  Denis Soulières, MD, Fred R.
Tumor Suppressor microRNAs Contribute to the Regulation of PD-L1 Expression in Malignant Pleural Mesothelioma  Steven C. Kao, PhD, Yuen Yee Cheng, PhD,
Treatment Outcomes by Tumor Histology in Eastern Cooperative Group Study E4599 of Bevacizumab with Paclitaxel/Carboplatin for Advanced Non-small Cell.
Dramatic Response to Pemetrexed in a Patient with Pneumonic-Type Mucinous Bronchioloalveolar Carcinoma  David H. Garfield, MD, Wilbur Franklin, MD  Journal.
Pneumonectomy is a valuable treatment option after neoadjuvant therapy for stage III non–small-cell lung cancer  Walter Weder, MD, Stéphane Collaud, MD,
Association of Phosphorylated Epidermal Growth Factor Receptor with Survival in Patients with Locally Advanced Non-small Cell Lung Cancer Treated with.
ERCC1 and BRAC1 mRNA Expression Levels in the Primary Tumor Could Predict the Effectiveness of the Second-Line Cisplatin-Based Chemotherapy in Pretreated.
Phase II Trial of Paclitaxel and Cisplatin in Patients with Extensive Stage Small Cell Lung Cancer: Cancer and Leukemia Group B Trial 9430  Thomas E.
Genetic Determinants of Pemetrexed Responsiveness and Nonresponsiveness in Non- small Cell Lung Cancer Cells  Ming-Fang Wu, MD, PhD, Yi-Min Hsiao, PhD,
Liver Metastasis Is Associated with Poor Progression-Free Survival in Patients with Non–Small Cell Lung Cancer Treated with Nivolumab  Tomoko Funazo,
A Correlative Biomarker Analysis of the Combination of Bevacizumab and Carboplatin- Based Chemotherapy for Advanced Nonsquamous Non–Small-Cell Lung Cancer:
PI3K/mTOR Signaling in Mesothelioma Patients Treated with Induction Chemotherapy Followed by Extrapleural Pneumonectomy  Byron K.Y. Bitanihirwe, PhD,
An Updated Meta-Analysis of Randomized Controlled Trials Comparing Irinotecan/Platinum with Etoposide/Platinum in Patients with Previously Untreated.
Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion–Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations.
Laurence J. Egan, M.B., William J. Sandborn, M.D 
Detection of Circulating Lung Cancer Cells with Strong Thymidylate Synthase Reactivity in the Peripheral Blood of a Patient with Pulmonary Adenocarcinoma.
PI3K/mTOR Signaling in Mesothelioma Patients Treated with Induction Chemotherapy Followed by Extrapleural Pneumonectomy  Byron K.Y. Bitanihirwe, PhD,
LAG-3 Protein Expression in Non–Small Cell Lung Cancer and Its Relationship with PD- 1/PD-L1 and Tumor-Infiltrating Lymphocytes  Yayi He, MD, PhD, Hui.
Thymidylate Synthase Expression and Outcome of Patients Receiving Pemetrexed for Advanced Nonsquamous Non–Small-Cell Lung Cancer in a Prospective Blinded.
Novel Epidermal Growth Factor Receptor Mutation-Specific Antibodies for Non-small Cell Lung Cancer: Immunohistochemistry as a Possible Screening Method.
ALK Translocation in Non-small Cell Lung Cancer with Adenocarcinoma and Squamous Cell Carcinoma Markers  Samuel J. Klempner, MD, David W. Cohen, MD, Daniel.
Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma  Kyuichi Kadota, MD, PhD, Jun-ichi Nitadori, MD, PhD, Hideki Ujiie, MD, Daniel.
Impact of HER2 Gene and Protein Status on the Treatment Outcome of Cisplatin-Based Chemoradiotherapy for Locally Advanced Non-small Cell Lung Cancer 
Associations between TS, TTF-1, FR-α, FPGS, and Overall Survival in Patients with Advanced Non–Small-Cell Lung Cancer Receiving Pemetrexed Plus Carboplatin.
Pleurectomy/Decortication is Superior to Extrapleural Pneumonectomy in the Multimodality Management of Patients with Malignant Pleural Mesothelioma  Loïc.
Maintenance Therapy and Advanced Non–Small-Cell Lung Cancer: A Skeptic's View  Martin J. Edelman, MD, Thierry Le Chevalier, MD, Jean-Charles Soria, MD,
Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local.
KRAS Mutations in Advanced Nonsquamous Non–Small-Cell Lung Cancer Patients Treated with First-Line Platinum-Based Chemotherapy Have No Predictive Value 
Anaplastic Lymphoma Kinase Gene Rearrangements in Non-small Cell Lung Cancer are Associated with Prolonged Progression-Free Survival on Pemetrexed  D.
Tivantinib in Combination with Erlotinib versus Erlotinib Alone for EGFR-Mutant NSCLC: An Exploratory Analysis of the Phase 3 MARQUEE Study  Giorgio V.
Pharmacogenetic and Germline Prognostic Markers of Lung Cancer
Thymidylate Synthase Protein Expression by IHC and Gene Copy Number by SISH Correlate and Show Great Variability in Non–Small Cell Lung Cancer  Murry.
A Pathological Complete Response in Malignant Pleural Mesothelioma after Combination Chemotherapy with Carboplatin and Pemetrexed  Steven Chuan-Hao Kao,
Genetic Polymorphisms in Methylenetetrahydrofolate Reductase and Thymidylate Synthase and Risk of Pancreatic Cancer  Li Wang, Xiaoping Miao, Wen Tan,
Reduced Folate Carrier and Folylpolyglutamate Synthetase, but not Thymidylate Synthase Predict Survival in Pemetrexed-Treated Patients Suffering from.
Safety distance in the resection of colorectal lung metastases: A prospective evaluation of satellite tumor cells with immunohistochemistry  Stefan Welter,
Treatment Outcomes by Tumor Histology in Eastern Cooperative Group Study E4599 of Bevacizumab with Paclitaxel/Carboplatin for Advanced Non-small Cell.
An International Interpretation Study Using the ALK IHC Antibody D5F3 and a Sensitive Detection Kit Demonstrates High Concordance between ALK IHC and.
A Randomized, Phase II Trial of Two Dose Levels of Temsirolimus (CCI-779) in Patients with Extensive-Stage Small-Cell Lung Cancer Who Have Responding.
Concurrent Chemotherapy and Short Course Radiotherapy in Patients with Stage IIIA to IIIB Non-small Cell Lung Cancer Not Eligible for Radical Treatment:
Debby P. M. van den Bogaert, MD, Ellen M
Outcome after Pulmonary Metastasectomy: Analysis of 5 Years Consecutive Surgical Resections 2002–2006  Kåre Hornbech, MD, Jesper Ravn, MD, Daniel Andreas.
Long-Term Follow-Up of a Phase I/II Trial of Dose Escalating Three-Dimensional Conformal Thoracic Radiation Therapy with Induction and Concurrent Carboplatin.
Presentation transcript:

Folylpoly-Glutamate Synthetase Expression Is Associated with Tumor Response and Outcome from Pemetrexed-Based Chemotherapy in Malignant Pleural Mesothelioma  Daniel C. Christoph, MD, PhD, Bernadette Reyna Asuncion, MD, Celine Mascaux, MD, PhD, Cindy Tran, BSc, Xian Lu, PhD, Murry W. Wynes, PhD, Thomas C. Gauler, MD, Jeremias Wohlschlaeger, MD, Dirk Theegarten, MD, Volker Neumann, PhD, Rodrigo Hepp, MD, Stefan Welter, MD, Georgios Stamatis, MD, Andrea Tannapfel, MD, Martin Schuler, MD, Wilfried E. Eberhardt, MD, Fred R. Hirsch, MDPhD  Journal of Thoracic Oncology  Volume 7, Issue 9, Pages 1440-1448 (September 2012) DOI: 10.1097/JTO.0b013e318260deaa Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Pemetrexed's mechanism of action: After transfer into cells, pemetrexed undergoes polyglutamylation. Both the nonglutamated and as the polyglutamated forms are able to inhibit DHFR, GARFT, and TS. Figure according to36. AMP, adenosine monophosphate; DHF, dihydrofolate; DHFR, dihydrofolate reductase; dTMP, deoxythymidine monophosphate; dUMP, deoxyuridine monophosphate; FPGS, folylpoly-γ-glutamate synthetase; GARFT, glycinamide ribonucleotide formyltransferase; GGH, gamma-glutamyl hydrolase; Gln, glutamine; GMP, guanosine monophosphate; IMP, inosine monophosphate; PCFT, proton-coupled folate transporter; PPRP, phosphoribosyl pyrophosphate; RFC, reduced folate carrier; THF, tetrahydrofolate; TS, thymidylate synthase. Journal of Thoracic Oncology 2012 7, 1440-1448DOI: (10.1097/JTO.0b013e318260deaa) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 A to H, Examples of IHC for FPGS and TS in MPM samples with different protein expressions. A to D, IHC with an antibody against FPGS: (A) hepatocellular carcinoma was used as positive control; (B) weakly stained MPM sample (H-score of 90); (C) moderately stained MPM sample (H-score of 170); and (D) strongly stained MPM sample (H-score of 290). E to -H, IHC with an antibody against TS (dilution 1:10); (E) colorectal carcinoma was used as positive control; (F) weakly stained MPM sample (H-score of 90); (G) moderately stained MPM sample (H-score of 170); and (H) strongly stained MPM sample (H-score of 290). Magnification 1:400. IHC, immunohistochemistry; FPGS, folylpoly-γ-glutamate synthetase; TS, thymidylate synthase; MPM, malignant pleural mesothelioma. Journal of Thoracic Oncology 2012 7, 1440-1448DOI: (10.1097/JTO.0b013e318260deaa) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 A to D, Associations between protein expression of FPGS and (A) PFS or (B) OS; associations between protein expression of TS and (C) PFS or (D) OS. FPGS, folylpoly-γ-glutamate synthetase; PFS, progression-free survival; H-Score, Hybrid-Score; OS, overall survival; TS, thymidylate synthase; IMIG, International Mesothelioma Interest Group; HR, hazard ratio; CI, confidence interval. Journal of Thoracic Oncology 2012 7, 1440-1448DOI: (10.1097/JTO.0b013e318260deaa) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions