Abstract

Squamous cell carcinoma of the head and neck (SCCHN) is known to develop through complex genetic and epigenetic alterations in genes that control cell proliferation, cell cycle, and cell survival. One set of genes that shows frequently altered expression are genes for growth factors and their receptors, including Epidermal Growth Factor Receptor (EGFR). G-protein- coupled receptors (GPCRs) have been shown to activate the EGFR in SCCHN, resulting in increased proliferation and invasion. This proposal will address the effect on SCCHN cell growth and survival of GPCR signaling cascades that show a dual mechanism: one that is EGFR-independent, as well as one that is integrated with the EGFR. Our preliminary results suggest that two GPCR systems, prostaglandin E2 (PGE2) and its receptors, and bradykinin (BK) and its receptors, stimulate SCCHN proliferation by this dual mechanism. The overall goal of this proposal is to demonstrate the mechanism and importance of signaling through PGE2 and BK in head and neck cancer proliferation, and develop a rationale for combining inhibitors of these GPCR pathways with EGFR inhibitors for the treatment of SCCHN. The long-term goal is to design a clinical trial combining EGFR inhibitors with inhibitors of PGE2 or BK for head and neck cancer patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA097190-03
Application #
7267743
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
3
Fiscal Year
2006
Total Cost
$205,379
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit et al. (2018) Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma. Cancer 124:84-94
Santuray, Rodell T; Johnson, Daniel E; Grandis, Jennifer R (2018) New Therapies in Head and Neck Cancer. Trends Cancer 4:385-396
Liu, Zhuqing; McMichael, Elizabeth L; Shayan, Gulidanna et al. (2018) Novel Effector Phenotype of Tim-3+ Regulatory T Cells Leads to Enhanced Suppressive Function in Head and Neck Cancer Patients. Clin Cancer Res 24:4529-4538
Lu, Shanhong; Concha-Benavente, Fernando; Shayan, Gulidanna et al. (2018) STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV+ status in head and neck cancer. Oral Oncol 78:186-193
Nikiforova, Marina N; Mercurio, Stephanie; Wald, Abigail I et al. (2018) Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules. Cancer 124:1682-1690
Zhong, Qian; Liu, Zhi-Hua; Lin, Zhi-Rui et al. (2018) The RARS-MAD1L1 Fusion Gene Induces Cancer Stem Cell-like Properties and Therapeutic Resistance in Nasopharyngeal Carcinoma. Clin Cancer Res 24:659-673
Ma, Jing; Salamoun, Joseph; Wipf, Peter et al. (2018) Combination of a thioxodihydroquinazolinone with cisplatin eliminates ovarian cancer stem cell-like cells (CSC-LCs) and shows preclinical potential. Oncotarget 9:6042-6054
Hartman, Douglas J; Ahmad, Fahad; Ferris, Robert L et al. (2018) Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma. Oral Oncol 86:278-287
Pai, Sara I; Jack Lee, J; Carey, Thomas E et al. (2018) HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers. Oral Oncol 77:92-97
Shayan, Gulidanna; Kansy, Benjamin A; Gibson, Sandra P et al. (2018) Phase Ib Study of Immune Biomarker Modulation with Neoadjuvant Cetuximab and TLR8 Stimulation in Head and Neck Cancer to Overcome Suppressive Myeloid Signals. Clin Cancer Res 24:62-72

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