Identified molecular targets that are functionally involved in the metastatic conversion of cancer cells.

Background  |  Applications  |  Advantages  |  Patents and Publications  |  Technology Reference Number

Background

Researchers at California Pacific Medical Center Research Institute (CPMC-RI) and Berkeley Lab have discovered Id-1, a transcriptional factor that can be used as a target for suppressing aggressive and metastatic cancer cells. Id-1 can also serve as a reliable marker for cancer progression, invasion, and metastasis, allowing for accurate diagnoses and prognoses and therefore more appropriate therapies.
Based on previous collaborative research with Judith Campisi of Berkeley Lab, Pierre-Yves Desprez and colleagues at CPMCRI have shown in pre-clinical studies that human metastatic breast cancer cells become significantly less invasive in culture and less metastatic in vivo when the Id-1 protein is down-regulated by antisense RNA directed against the Id-1 gene. In a highly successful proof-of-concept experiment, these investigators targeted Id-1 expression systemically in tumor-bearing mice with a non-viral approach using liposomes, significantly reducing Id-1 levels and simultaneously the spread of breast cancer cells. These results point to the Id-1 gene as an extremely promising target for developing therapies to reduce breast cancer metastasis.

Desprez and Campisi earlier determined that ectopic expression of Id-1 in murine mammary epithelial cells results in loss of differentiation and gain of invasive and proliferative abilities. Using immunohistochemistry, they found high levels of expression of the Id-1 protein in breast tumor biopsies from patients with aggressive cancer and low levels in ductal carcinomas, which are known to be noninvasive. In addition, ectopic expression of Id-1 in a noninvasive human breast cancer cell line rendered it invasive.



CPMCRI studies of Id-1 demonstrated that Id-1 can be down regulated, not only by RNA inhibition, but also by exogenous agents. This finding has an extremely high clinical value since the researchers have identified a compound that can inhibit both cancer cell proliferation and invasiveness. Furthermore, recent studies have shown that down regulation of Id-1 has an inhibitory affect on the metastatic progression of cancers of various tissue origins. This finding demonstrated that Id-1 plays important regulatory roles in cellular pathways critical to cancer.

For more information see the Lawrence Berkeley National Laboratory Berkeley lab webpage describing this technology and link to the publications below.


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Applications

Therapeutic target for the suppression of invasive and metastatic cancers

Diagnostic and/or prognostic marker for invasive and metastatic cancers

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Advantages

Identifies Id-1, a key transcriptional regulator, as a target for the development of cancer treatment that could be highly effective and more discriminate than those currently available

Provides a highly accurate marker for invasive and metastatic cancers

Inhibition of Id-1 protein would beneficially affect multiple aspects of cancer progression

Since Id-1 is scarce in most mature adult tissues, a majority of normal cells would not be affected by systemic therapy targeting this gene.

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Patents and Publications

Patent Pending
Available for licensing or collaborative research

Publications:

Fong, S., Itahana, Y., Sumida, T., Singh, J., Coppe, J.P., Liu, Y., Richards, P.C., Bennington, J.L., Lee, N.M., Debs, R.J., Desprez, P.Y.," Id-1 as a Molecular Target in Therapy for Breast Cancer Cell Invasions and Metastasis," Proc. Natl. Acad. Sci., 2003, 100, 13543-48.

Itahana, Y., Singh, J., Sumida, T., Coppe, J.P., Parrinello, S., Bennington, J.L., Desprez, P.Y., " Role of Id-2 in the Maintenance of a Differentiated and Noninvasive Phenotype in Breast Cancer Cells,"Cancer Res., 2003, 63, 7098-105.

Lin, C.Q., Singh, J., Murata, K., Itahana, Y., Parrinello, S., Liang, S.H., Gillett, C.E., Campisi, J., Desprez, P.Y., " A Role for Id-1 in the Aggressive Phenotype and Steroid Hormone Response of Human Breast Cancer Cells," Cancer Res., 2000, 60, 1332-40.

Related Article:

Andy J. Minn, Gaorav P. Gupta, Peter M. Siegel, Pual D. Bos, Weiping Shu, Dilip D. Giri, Agnes Viale, Adam B. Olshen, William L. Gerald, and Joan Massague, "Genes that Mediate Breast Cancer Metastasis to Lung" Nature, 2005, 436, 518-524.

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Technology Reference Number

D-051101


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