Method and compositions for inhibiting tumorigenesis

• US 7,741,298 B2
• Filed: 08/31/2004
• Issued: 06/22/2010
• Est. Priority Date: 06/20/1997
• Status: Expired due to Fees

• Current Assignee: New York University Medical Center (New York University)
• Original Assignee: New York University
• Inventors: Altaba, Ariel Ruiz i, Rom, William, Wong, Kam-Meng Tchou, Sanchez, Pilar
• Primary Examiner(s): WHITEMAN, BRIAN A
• Application Number:
  US10/930,723
• Publication Number:
  US 20050112707A1
• Time in Patent Office: 2,121 Days
• Field of Search: 514/44
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/41 Hedgehog proteins; Cyclopamine (inhibitor)
• CPC Class Codes: C12N 2506/08 from cells of the nervous system
• CPC Class Codes: C12N 5/0619 Neurons
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/5082 Supracellular entities, e.g. tissue, organisms
• 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 using agents that inhibit the sonic hedgehog and GLI signaling pathway, including agents that inhibit GLI expression, synthesis and/or function. The present invention also relates to particular biomarkers that can be used in the diagnosis and prognosis of cancer. Methods of treating cancer, including glioblastomas, medulloblastomas, basal cell carcinomas, prostate cancer and small cell and non-small cell lung cancer are also provided using small organic compounds, siRNAs and blocking antibodies that inhibit or block the SHH/GLI pathway.

Claims

1. A method of inducing apoptosis in an in vitro tumor cell that expresses a GLI protein comprising administering an siRNA molecule comprising SEQ ID NO:

29 to the tumor cell, wherein said administering results in tumor cell death.

2. The method of claim 1, wherein said tumor cell is selected from the group consisting of gliomas, medulloblastomas, primitive neuroectodermal tumors (PNETS), basal cell carcinoma, small cell lung cancers, non-small cell lung cancers, tumors of the gastrointestinal tract, rhabdomyosarcomas, soft tissue sarcomas, pancreatic tumors and prostate tumors.

3. A method of inhibiting tumor cell growth or proliferation of a tumor cell in vitro, wherein said tumor cell expresses a GLI protein, said method comprising administering an siRNA molecule comprising SEQ ID NO:

29 to the tumor cell, wherein said administering results in induction of apoptosis in said tumor cell and an increased sensitivity to chemotherapeutic agents.

4. The method of claim 3, wherein siRNA molecule is SEQ ID NO: