NF-kappaB in pathogenesis and therapy of head and neck cancer

Van Waes, Carter

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-mTOR, and Notch pathways as candidate genetic drivers for aberrant NF-kB activation and defects in death signaling. A clinical trial with PI3K-mTOR inhibitor rapamycin has completed accrual and published. A multi-center trial targeting IAPs in the classical TNF-NF-kB pathway in combination with re-irradiation has been approved and opened. 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 #: 1ZIADC000016-26
• Application #: 9998620
• Support Year: 26
• Fiscal Year: 2019

Institution

• Name: National Institute on Deafness and Other Communication Disorders

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

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

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

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