Therapeutic and diagnostic applications based on the role of the CXCR-4 gene in tumorigenesis

Abstract

The present invention relates to the identification of a novel role of CXCR-4 in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of CXCR-4 in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for CXCR-4. Further, the present invention relates, in part, to the Applicants' surprising discovery that the inhibition of CXCR-4 gene expression or the inhibition of CXCR-4 activity in transformed cells reverses the transformed phenotype.

Description

1. FIELD OF THE INVENTION [0001] The present invention relates to the identification of a novel role for the CXCR-4 gene in tumorigenesis, in particular primary brain, breast and colon tumorigenesis. The present invention is related to the role of CXCR-4 nucleic acids and polypeptides as diagnostic tools to indicate a pre-cancerous condition or cancer, and therapeutic agents based thereon to inhibit CXCR-4 gene expression and / or activity as a method of treating and / or preventing tumorigenesis. 2. BACKGROUND OF THE INVENTION [0002] 2.1. Brain Tumors [0003] Brain tumors are among the leading cause of death among young children and adults. A survey by the American Cancer Society has documented that 13,300 people died of brain tumors in 1995 and predicated that over 17,900 would die in 1996 (Parker et al., 1996, CA Cancer J. Clin., 46:5-28). The number of deaths due to brain tumors has been increasing at a significant rate each year. On average, 25,000 Americans are diagnosed with brain...

AI Technical Summary

Benefits of technology

[0012] The present invention is based, in part, on the Applicants' surprising discovery that the CXCR-4 nucleotide sequence and encoded gene product is expressed at high levels in glioblastoma multiforme tissue, as well as, certain other forms of tumors and cancers.

[0013] In one embodiment, the present invention encompasses nucleotide sequences complementary to the nucleotide sequence of CXCR-4, such as primers, fragments or antisense nucleotides which may be used to determine the level of CXCR-4 expression in a tissue or cell culture sample as prognostic of a pre-cancerous or transformed cell phenotype; or to inhibit CXCR-4 expression as a method of treating or preventing a pre-cancerous or transformed cell phenotype. In a specific embodiment, the CXCR-4 gene is a human gene and the CXCR-4 protein is a human protein.

[0014] The present invention also encompasses inhibitors of CXCR-4 activities related to cellular transformation. CXCR-4 is a known G protein coupled receptor involved in transducing signals. The present invention encompasses peptide fragments or antagonist

Problems solved by technology

The exact series of events that lead to initiation or progression of glioblastoma are not known at present and useful markers for early detection of brain tumors are lacking.

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