Malignant pleural mesothelioma (MPM) is a highly lethal cancer for which effective therapy is lacking. Even the basic elements to treatment for this malignancy such as expedient diagnosis and accurate prognosis remain challenging and aggressive surgical extirpation is required for definitive staging and prognosis. We have previously described a novel technique using gene expression ratios to translate whole genome expression studies into clinically relevant tests that can accurately predict many clinical parameters such as diagnosis and prognosis in cancers. Specifically, we developed a test to distinguish between MPM and lung cancer and another test to,predict outcome in MPM patients undergoing surgery. These ratio-based tests require small amounts of tumor RNA, to predict in a statistically significant manner diagnosis as well as clinical outcome for patients undergoing surgery for MPM. We propose to expand the diagnostic capability of these tests by identifying additional genes to make the correct diagnosis whenever MPM is suspected. This methodology can serve as a template for a genomic . differential diagnosis algorithm to be an adjunct for pathology. We will then refine and validate these tests on additional specimens. We also propose to refine and develop the methodology so that specimens obtained minimally invasively or while using image-guided fine needle aspiration can be appropriately tested. To bring the prognostic and diagnostic tests to bedside they need to be made relevant to actual patient management, be standardized and be validated, preferably in a multi-center setting. We propose to prospectively validate the prognostic tests both with fine needle aspiration and minmally invasive biopsies in additional patients enrolled prospectively in clinical trials at our institution and in a multi center study. The proposed work will capitalize on new technology that can measure the expression (RNA) of the entire tumor genome to develop new tests that can be easily applied to patients. In addition to providing new tests that will alter the management of MPM patients--by eventually making surgery for diagnosis unecessary and save certain patientsfrom unecessary major surgery- this work will allow us to develop a diagnostic, prognostic and treatment directing platform that can be ultimately used for other cancers and human diseases to allow individual genome directed therapy for cancer and other diseases.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA120528-05
Application #
7776923
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Kim, Kelly Y
Project Start
2006-04-07
Project End
2011-08-31
Budget Start
2010-03-01
Budget End
2011-08-31
Support Year
5
Fiscal Year
2010
Total Cost
$301,617
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Lapidot, Moshe; Freyaldenhoven, Samuel; Bueno, Raphael (2018) New concepts in the treatment of malignant pleural mesothelioma. J Thorac Dis 10:1283-1285
Vivero, Marina; Bueno, Raphael; Chirieac, Lucian R (2018) Clinicopathologic and genetic characteristics of young patients with pleural diffuse malignant mesothelioma. Mod Pathol 31:122-131
Kindler, Hedy L; Ismaila, Nofisat; Armato 3rd, Samuel G et al. (2018) Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 36:1343-1373
De Rienzo, Assunta; Cook, Robert W; Wilkinson, Jeff et al. (2017) Validation of a Gene Expression Test for Mesothelioma Prognosis in Formalin-Fixed Paraffin-Embedded Tissues. J Mol Diagn 19:65-71
Bueno, Raphael; Stawiski, Eric W; Goldstein, Leonard D et al. (2016) Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet 48:407-16
De Rienzo, Assunta; Archer, Michael A; Yeap, Beow Y et al. (2016) Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma. Cancer Res 76:319-28
Baldini, Elizabeth H; Richards, William G; Gill, Ritu R et al. (2015) Updated patterns of failure after multimodality therapy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 149:1374-81
Tempany, Clare M C; Jayender, Jagadeesan; Kapur, Tina et al. (2015) Multimodal imaging for improved diagnosis and treatment of cancers. Cancer 121:817-27
Kanteti, Rajani; Dhanasingh, Immanuel; Kawada, Ichiro et al. (2014) MET and PI3K/mTOR as a potential combinatorial therapeutic target in malignant pleural mesothelioma. PLoS One 9:e105919
Opitz, Isabelle; Bueno, Raphael; Lim, Eric et al. (2014) Biomolecular and clinical practice in malignant pleural mesothelioma and lung cancer: what thoracic surgeons should know. Eur J Cardiothorac Surg 46:602-6

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