Abstract: A class of antisense agents having a distributed guanidinium peptide nucleic acids (GPNA) backbone which has excellent uptake into mammalian cells, can bind to the target DNA or RNA in a highly sequence specific manner and can resist nucleases and proteases both outside and inside the cell(s) of interest. In one embodiment, either systemic or intratumoral administration of antisense Epidermal Growth Factor Receptor (“EGFR”) GPNA oligonucleotides is believed to downmodulate EGFR levels, thus in turn to reduce head and neck squamous cell carcinoma tumor growth, which has been confirmed to date both in vitro and in vivo.
Type:
Grant
Filed:
May 13, 2011
Date of Patent:
May 10, 2016
Assignees:
EYE & EAR FOUNDATION, UNIVERSITY OF PITTSBURGH OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION, CARNEGIE MELLON UNIVERSITY
Inventors:
Jennifer Rubin Grandis, Sufi Mary Thomas, Danith H. Ly
Abstract: A cancer prognostic having particular utility in the prognosis of head and neck squamous cell cancer, in which the expression levels of either or both of Transforming Growth Factor Alpha (TGF-.alpha.) or Epidermal Growth Factor Receptor (EGFR) are assayed directly from a sample of tumor tissue. The expression level once quantitated is normalized as to standard, and the standardized expression level is compared to the prognostic threshold of about 83% of standard for TGF-.alpha. or of about 23% of standard for EGFR, or the corresponding upper threshold of the "low" tertile regardless of how calculated. Virtually all if not all patients demonstrating this low expression level survive at least five years after initial diagnosis, assuming completion of treatment with standard surgical tumor excision and radiation protocols for squamous cell head and neck cancer. Whether an individual patient's expression levels of TGF-.alpha.