Public Health Relevance

Lung cancers that harbor oncogenic mutations in the KRAS oncogene are refractory to both cytotoxic and targeted chemotherapy. This proposal focuses validating the NF-KB regulator TBK1 and NF-KB signaling as targets in KRAS-dependent lung cancers. These studies will not only provide insight into the biology of the NF-KB in lung cancer but will serve as a foundation for translational studies for the development of novel therapeutic agents.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA154303-02
Application #
8559664
Study Section
Special Emphasis Panel (ZCA1-GRB-P)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$236,605
Indirect Cost
$88,519
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Tan, Li; Gurbani, Deepak; Weisberg, Ellen L et al. (2017) Structure-guided development of covalent TAK1 inhibitors. Bioorg Med Chem 25:838-846
Tan, Li; Gurbani, Deepak; Weisberg, Ellen L et al. (2017) Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. Bioorg Med Chem 25:1320-1328
Deng, Jiehui; Wang, Eric S; Jenkins, Russell W et al. (2017) CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov :
Krall, Elsa B; Wang, Belinda; Munoz, Diana M et al. (2017) KEAP1 loss modulates sensitivity to kinase targeted therapy in lung cancer. Elife 6:
Adeegbe, Dennis O; Liu, Yan; Lizotte, Patrick H et al. (2017) Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer. Cancer Discov 7:852-867
Majkowska, Iwona; Shitomi, Yasuyuki; Ito, Noriko et al. (2017) Discoidin domain receptor 2 mediates collagen-induced activation of membrane-type 1 matrix metalloproteinase in human fibroblasts. J Biol Chem 292:6633-6643
Meyers, Robin M; Bryan, Jordan G; McFarland, James M et al. (2017) Computational correction of copy number effect improves specificity of CRISPR-Cas9 essentiality screens in cancer cells. Nat Genet 49:1779-1784
Wang, Belinda; Krall, Elsa Beyer; Aguirre, Andrew James et al. (2017) ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition. Cell Rep 18:1543-1557
Zhang, Haikuo; Qi, Jun; Reyes, Jaime M et al. (2016) Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer. Cancer Discov 6:1006-21
Yang, Shenghong; Imamura, Yu; Jenkins, Russell W et al. (2016) Autophagy Inhibition Dysregulates TBK1 Signaling and Promotes Pancreatic Inflammation. Cancer Immunol Res 4:520-30

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