Abstract

As part of The Cancer Genome Atlas group characterizing head and neck cancer, we have identified components of the classical and alternative NF-kB, PI3K, and Notch pathways as candidate genetic drivers for aberrant NF-kB activation and defects in death signaling. We have reported that decreased TRAF3 contributes to aberrant activation of the alternative NF-kB pathway, which promotes migration of HNSCC. We have shown Notch1 mediates non-canonical activation of IKKalpha and NF-kB signaling in cutaneous squamous cell carcinoma stem cells. A clinical trial with PI3K-mTOR inhibitor rapamycin has completed accrual and been submitted for publication. Studies using a genome wide RNAi screen employing NF-kB reporter lines have identified potential drug targets promoting NF-kB activation, under investigation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADC000016-25
Application #
9781311
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Deafness & Other Communication Disorders
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Zhang, Jialing; Chen, Tony; Yang, Xinping et al. (2018) Attenuated TRAF3 Fosters Activation of Alternative NF-?B and Reduced Expression of Antiviral Interferon, TP53, and RB to Promote HPV-Positive Head and Neck Cancers. Cancer Res 78:4613-4626
Quan, Xin Xin; Hawk, Nga Voong; Chen, Weiping et al. (2018) Targeting Notch1 and IKK? Enhanced NF-?B Activation in CD133+ Skin Cancer Stem Cells. Mol Cancer Ther 17:2034-2048
Zhang, Yiqun; Kwok-Shing Ng, Patrick; Kucherlapati, Melanie et al. (2017) A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. Cancer Cell 31:820-832.e3
Derakhshan, Adeeb; Chen, Zhong; Van Waes, Carter (2017) Therapeutic Small Molecules Target Inhibitor of Apoptosis Proteins in Cancers with Deregulation of Extrinsic and Intrinsic Cell Death Pathways. Clin Cancer Res 23:1379-1387
Chen, Tony; Zhang, Jialing; Chen, Zhong et al. (2017) Genetic alterations in TRAF3 and CYLD that regulate nuclear factor ?B and interferon signaling define head and neck cancer subsets harboring human papillomavirus. Cancer 123:1695-1698
Si, H; Lu, H; Yang, X et al. (2016) TNF-? modulates genome-wide redistribution of ?Np63?/TAp73 and NF-?B cREL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer. Oncogene 35:5781-5794
Eytan, Danielle F; Snow, Grace E; Carlson, Sophie et al. (2016) SMAC Mimetic Birinapant plus Radiation Eradicates Human Head and Neck Cancers with Genomic Amplifications of Cell Death Genes FADD and BIRC2. Cancer Res 76:5442-5454
Guven-Maiorov, Emine; Keskin, Ozlem; Gursoy, Attila et al. (2016) TRAF3 signaling: Competitive binding and evolvability of adaptive viral molecular mimicry. Biochim Biophys Acta 1860:2646-55
Moore, Ellen C; Cash, Harrison A; Caruso, Andria M et al. (2016) Enhanced Tumor Control with Combination mTOR and PD-L1 Inhibition in Syngeneic Oral Cavity Cancers. Cancer Immunol Res 4:611-20
Davis, Ruth J; Van Waes, Carter; Allen, Clint T (2016) Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer. Oral Oncol 58:59-70

Showing the most recent 10 out of 38 publications