Clinical Trial: DNA Analysis of Tumor Tissue Samples From Patients With Human Papilloma Virus-Associated Cancer of the Oropharynx

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Effect of PI3K Inhibition in HPV-Associated HNSCC

Brief Summary:

RATIONALE: Studying samples of tumor tissue in the laboratory from patients with cancer may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This laboratory study is looking at the DNA in tumor tissue samples from patients with human papilloma virus-associated cancer of the oropharynx.


Detailed Summary:

OBJECTIVES:

  • Analyze PIK3CA expression and mutation and p110α amplification and expression in tumor tissue samples from patients with human papilloma virus positive (HPV+) and human papilloma virus negative (HPV-) squamous cell carcinoma (SCC) of the oropharynx.
  • Determine proliferation and survival after PI3K inhibition in HPV(+) and HPV(-) oropharyngeal SCC cell lines and in HPV E6 and E7 expressing cells.
  • Determine proliferation and survival after PI3K inhibition in short-term cultures of tumor tissue samples from patients with HPV(+) and HPV(-) primary SCC of the oropharynx.

OUTLINE: Previously collected tumor tissue samples are analyzed for HPV DNA by PCR amplification and direct sequencing of PCR products; expression of E6 protein and relative expression of PIK3CA by qRT-PCR; amplification of PIK3CA by Southern blotting; mutation of PIK3CA; expression of p110α, phospho-AKT, total AKT, and FOXO1 by polyacrylamide gel electrophoresis (PAGE) and immunoblotting; and the effect of PI3K inhibition on cell cycle and apoptosis by flow cytometry. Pharmacological studies are performed on oropharyngeal squamous cell carcinoma cell lines and short-term cultures and HPV E6 and E7 expressing cells using LY 294002 in vitro to analyze response to PI3K inhibition. Results of response to PI3K inhibition will be correlated with HPV status, PIK3CA expression, amplification, and mutation, and p110α expression.

PROJECTED ACCRUAL: A total of 20 HPV(+) and 20 HPV(-) tumor tissue specimens from patients will be accrued for this study.


Sponsor: Vanderbilt University Medical Center

Current Primary Outcome:

  • PIK3CA expression and mutation and p110α amplification and expression in tumor tissue samples from patients with human papilloma virus positive (HPV+) and human papilloma virus negative (HPV-) squamous cell carcinoma (SCC) of the oropharynx
  • Proliferation and survival after PI3K inhibition in HPV(+) and HPV(-) oropharyngeal SCC cell lines and in HPV E6 and E7 expressing cells
  • Proliferation and survival after PI3K inhibition in short-term cultures of tumor tissues from patients with HPV(+) and HPV(-) primary SCC of the oropharynx


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Vanderbilt University Medical Center

Dates:
Date Received: May 9, 2009
Date Started: April 2006
Date Completion:
Last Updated: March 10, 2017
Last Verified: March 2017