University of Pittsburgh Cancer Institute (UPCI)

Cell Signaling

SCCHN Signaling The HNCP signaling group has a strong research focus on the role of epidermal growth factor receptor (EGFR) and signal transducers and activators of transcription (STAT) signaling in head and neck cancer development and progression, and is testing how modulators of these growth promoters may improve patient outcome. In addition, HNCP members are exploring the mechanisms, and potential inhibitors, of angiogenesis.




Selected Publications

  • Epidermal growth factor receptor (EGFR) overexpression is correlated with decreased survival in head and neck cancer (HNC) where the addition of EGFR inhibition to standard chemoradiation approaches has improved treatment responses. However, the basis for the limited efficacy of EGFR inhibitors in HNC is incompletely understood. G-protein-coupled receptors (GPCR) have been shown to be overexpressed in HNC where GPCR activation induces HNC growth via both EGFR-dependent and -independent pathways. Results suggest that increased phosphorylation of p70S6K in the EGFR inhibitor cetuximab-treated patients may be due to increased GPCR signaling. Therefore, the addition of p70S6K targeting strategies may improve treatment responses to EGFR inhibition (Bhola et.al., Clin Cancer Res. 2011 Aug 1;17(15):4996-5004).
  • Chemoprevention of head and neck squamous cell carcinoma (HNSCC), a disease associated with high mortality rates and frequent occurrence of second primary tumor (SPT), is an important clinical goal. The epidermal growth factor receptor (EGFR)-signal transducer and activator of transcription (STAT)-3 signaling pathway is known to play a key role in HNSCC growth, survival, and prognosis, thereby serving as a potential therapeutic target in the treatment of HNSCC. Erlotinib, a small molecule inhibitor of the EGFR, when supplemented in diet exhibited a 69% decrease in incidence of preneoplastic and neoplastic lesions in chemical carcinogen-treated mice compared with mice on the control diet (Leeman-Neill et.al., Cancer Prev Res (Phila). 2011 Feb;4(2):230-7).
  • Acquired resistance to cetuximab, a chimeric epidermal growth factor receptor (EGFR)-targeting monoclonal antibody, is a widespread problem in the treatment of solid tumors. Results from a recent study suggest that the use of dual EGFR-HER2 kinase inhibitors can enhance responses to cetuximab, perhaps in part due to downregulation of 611-CTF, a C-terminal fragment of HER2 (Quesnelle et.al., Clin Cancer Res. 2011 Sep 15;17(18):5935-44).

Members

Chiosea, Simon, MD
Pathology
Johnson, Jonas, MD, FACS
Otolaryngology
Duvvuri, Uma, MD, PhD
Otolaryngology
Kim, Steve, PhD
Otolaryngology
Egloff, Ann, PhD
Otolaryngology
Myers, Eugene, MD
Otolaryngology
Ferris, Robert L., MD, PhD, FACS
Otolaryngology
Nikiforov, Yuri MD, PhD
Pathology
Gooding, William, MS
Biostatistics
Saunders, William, PhD
Biological Sciances
Grandis, Jennifer, MD, FACS
Otolaryngology
Seethala, Raja, MD, FASCP
Pathology
Johnson, Daniel, PhD
Medicine
Sorkin, Alexander, PhD
Cell Biology & Physiology