Project 1: Translational studies in lung cancer. To investigate miRNA influence on prognosis and prediction of effect of adjuvant chemotherapy in radically resected non-small cell lung cancer (NSCLC) in the International Adjuvant Lung Cancer Trial (IALT), a randomized study of adjuvant chemotherapy vs. follow-up. To investigate associations of miRNAs and prognosis in lung adenocarcinoma vs. squamous cell carcinoma. To investigate if miR-21 expression is increased in EGFR mutant tumors. To investigate if miR-34a,b,c expression levels correlate with p53 status and p53 mutant tumors have reduced miR-34 expression. To investigate if let-7 has a stronger association with prognosis in wild-type K-Ras tumors. The study has been completed and published. None of the seven selected microRNAs had a significant correlation with survival or association with K-RAS or P53 mutations. Project 2: Translational studies in thymic malignancies. To study the incidence of thymomas compared to matched controls and also to assess survival patterns as well as risks of autoimmune diseases and secondary malignancies using a comprehensive population-based study. This study has been completed and published. The major findings was that younger patients have a poorer prognosis and that thymomas have a worse prognosis than matched controls. Project 3: Clinical studies in thoracic malignancies. To develop target agents that overcome resistance to EGFR TKIs, in particular, second-generation EGFR inhibitors, Met inhibitors, and HSP-90 inhibitors. Investigate novel agents in patients with advanced thymoma and thymic carcinoma. Study the tumor and surrogate markers of activity, to better identify patients who may benefit from treatment with targeted agents. Project 4: Therapeutic targets in thymic malignancies To perform CGH and RNA sequencing and exome sequencing on paraffin-embedded tumors and frozen tumors from patients with advanced thymic malignancies. To identify potential gene modifications (amplifications, translocations, mutations, etc.) that might be relevant as prognostic factors and or targets for systemic treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011269-04
Application #
8763425
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2013
Total Cost
$1,084,453
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Giaccone, Giuseppe; Wang, Yisong (2011) Strategies for overcoming resistance to EGFR family tyrosine kinase inhibitors. Cancer Treat Rev 37:456-64
Harada, Taishi; Yatabe, Yasushi; Takeshita, Masafumi et al. (2011) Role and relevance of TrkB mutations and expression in non-small cell lung cancer. Clin Cancer Res 17:2638-45
Lemos, Clara; Giovannetti, Elisa; Zucali, Paolo A et al. (2011) Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients. Pharmacogenomics 12:159-70
Harada, T; Lopez-Chavez, A; Xi, L et al. (2011) Characterization of epidermal growth factor receptor mutations in non-small-cell lung cancer patients of African-American ancestry. Oncogene 30:1744-52
Killian, J Keith; Walker, Robert L; Suuriniemi, Miia et al. (2010) Archival fine-needle aspiration cytopathology (FNAC) samples: untapped resource for clinical molecular profiling. J Mol Diagn 12:739-45
Wang, Yisong; Trepel, Jane B; Neckers, Leonard M et al. (2010) STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. Curr Opin Investig Drugs 11:1466-76
Hwang, Jin-Hyeok; Voortman, Johannes; Giovannetti, Elisa et al. (2010) Identification of microRNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLoS One 5:e10630
Kelly, Ronan J; Carter, Corey; Giaccone, Giuseppe (2010) Personalizing therapy in an epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small-cell lung cancer using PF-00299804 and trastuzumab. J Clin Oncol 28:e507-10
Petrini, Iacopo; Zucali, Paolo A; Lee, Hye Seung et al. (2010) Expression and mutational status of c-kit in thymic epithelial tumors. J Thorac Oncol 5:1447-53
Moody, Terry W; Berna, Marc J; Mantey, Samuel et al. (2010) Neuromedin B receptors regulate EGF receptor tyrosine phosphorylation in lung cancer cells. Eur J Pharmacol 637:38-45

Showing the most recent 10 out of 14 publications