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Recapitulating Year One of the Hilton Ludwig Cancer Metastasis Initiative

A year ago, the Institute formed a partnership with the Conrad N. Hilton Foundation to create the Hilton-Ludwig Cancer Metastasis Initiative (HLCMI), an extensive research effort specifically focused on metastasis. The HLCMI has provided the strategies and resources needed for a diverse group of LICR investigators and collaborators to join forces in attempting to understand metastasis, the direct cause of nearly all cancer deaths.

Metastasis is the outcome of multiple biological processes and signaling pathways gone awry. Once cancer has metastasized, the opportunity to control the disease diminishes or disappears. The identification of molecules that might be targeted to prevent metastasis, or to diagnose patients with highly metastatic tumors, is complicated by the tremendous complexity of this disease manifestation. Drs. Andy Simpson (Scientific Director) and Lloyd Old (Chairman) conceived a four-part approach to investigate metastasis that includes tumor banks, molecular analysis of tumor samples, a metastasis database, and meetings.

To identify molecular alterations that drive metastasis, it is critical for investigators to have access to tissue banks containing samples of normal cells and tumors that are ‘matched’ (derived from the same patient) and for which there is detailed knowledge about the patient’s disease history and response to treatment. Hundreds of matched samples have been collected from patients with melanoma and brain, colon and ovarian cancers, along with a large number of patient-derived cell lines that are also matched with normal samples.

The HLCMI investigators are accessing the tissue banks to conduct sequencing, transcriptomic and immunohistochemistry analyses. Much of the molecular analysis is being conducted in collaboration with LICR Affiliate Dr. Robert Strausberg at the J. Craig Venter Institute. A particular emphasis is being given to the analysis of cancer/testis (CT) genes, which are expressed in the germ-line and in some cancers but not in normal tissues, as LICR has invested many years of research on the development of therapeutic cancer vaccines based on CT gene products. Recent research findings suggest that some CT genes play a direct role in metastasis, and there is also evidence that CT gene expression is higher in metastatic samples. A comprehensive analysis of CT genes might characterize the relationship between CT genes and metastasis and also reveal whether tumors carrying mutations in these genes are less susceptible to treatment with cancer vaccines. Read more about research on CT genes in the Melanoma and Ovarian Cancer Meeting Report, NewsLink September 2007.

Perhaps the most challenging component of the HLCMI is an effort to collate a vast amount of data from the literature into a form that can be readily synthesized and accessed by cancer researchers. Dr. Nick Papanikolaou, HLCMI Bioanalyst, is currently populating a metastasis database—known internally as ‘CONRAD’—with data on genes that have been linked to cancer and metastasis. A complementary and more experimental approach is being developed by a second HLCMI Bioanalyst, Dr. Anna Divoli, who is working with Prof. Andrey Rzhetsky at the University of Chicago’s Institute for Genomics and Systems Biology. They will create computational text-mining algorithms that interpret data and concepts from the literature by parsing research documents for metastasis-oriented language.

The HLCMI has thus far funded five meetings to coordinate collaborative research efforts in specific disease areas. There have been meetings focused on brain, breast and colon cancers, and a joint meeting for melanoma and ovarian cancer. A fifth meeting of investigators engaged in the high-throughput sequencing and transcriptomic projects was held in New York in March, 2008."

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