Methods and compositions for inhibiting tumorigenesis

• US 7,709,454 B2
• Filed: 04/20/2006
• Issued: 05/04/2010
• Est. Priority Date: 06/20/1997
• Status: Expired due to Fees

• Current Assignee: New York University
• Original Assignee: New York University
• Inventors: Stecca, Barbara, Ruiz I Altaba, Ariel
• Primary Examiner(s): ZARA, JANE J
• Application Number:
  US11/407,702
• Publication Number:
  US 20070009530A1
• Time in Patent Office: 1,475 Days
• Field of Search: 435/6, 435/91.31, 435/455, 435/91.1, 435/375, 514/1, 514/2, 514/44, 536/23.1, 536/24.5
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: G01N 33/5743 of skin, e.g. melanoma

Abstract

The present invention relates to compounds, small interfering RNAs and compositions and methods of inhibiting tumorigenesis and methods of inhibiting tumor cell growth and proliferation using agents that inhibit the hedgehog and Gli signaling pathway, including agents that inhibit GLI synthesis and/or function. The present invention also relates to particular biomarkers that can be used in the diagnosis and prognosis of melanomas. Methods of treating cancer, including melanoma are also provided using small organic compounds, siRNAs and blocking antibodies that inhibit or block the SHH/GLI pathway. In addition, the use of agents that inhibit other signaling pathways is contemplated for use as second agents to be used in conjunction with the inhibitors of the GLI pathway.

Claims

1. A method for inhibiting the synthesis, expression or activity of a GLI protein in a cell comprising, contacting the cell with or introducing into the cell an inhibitor or antagonist of GLI synthesis or expression or activity, wherein the inhibitor or antagonist is the nucleic acid sequence set forth in SEQ ID NO:

1 wherein the contacting or introducing results in inhibition of synthesis, expression or activity of the GLI protein in the cell.

2. The method of claim 1, wherein the introducing further results in inhibition of cellular proliferation or inhibition of tumorigenesis.

3. The method of claim 2, wherein the inhibition of cellular proliferation occurs in a melanocyte, a benign or atypical nevus, a primary melanoma, or a metastatic melanoma.

4. The method of claim 1, wherein the cell is a tumor cell.

5. The method of claim 3, wherein the tumor cell is selected from the group consisting of a melanoma, a melanosarcoma and an amelanotic sarcoma.