Cancer Metastasis Regulators found to work with Cellular Network

A new study published in April, 2014 in the journal PLoS One by researchers in the Department of Pediatrics and UCSD School of Medicine has identified a new group of proteins within the macrophage which regulate cancer metastasis suggesting a new avenue for potential treatment of metastatic disease.

Metastasis is the most common cause of cancer-related death in the world. Researchers have long sought to discover the root fundamental regulators of cancer metastasis in an effort to find therapies that would block this clinically frequent and life threatening condition.  Moreover, recent evidence suggests that it involves both the cancer cells and there surrounding supporting cellular network, termed the tumor stroma or microenvironment. The stroma is made up of inflammatory cells like macrophages. A new study published in April, 2014 in the journal PLoS One by researchers in the Department of Pediatrics and UCSD School of Medicine has identified a new group of proteins within the macrophage which regulate cancer metastasis suggesting a new avenue for potential treatment of metastatic disease.

In the new paper, a multidisciplinary team led by principal investigator, Donald L. Durden, MD, PhD, Professor of pediatrics and Vice Chair for Research in the Dept. of Pediatrics at UC San Diego School of Medicine discovered a new signaling pathway within the macrophage which regulates cancer cell metastasis. In animal genetic experiments, knockout of one specific gene, Rac2,  prevented the process of tumor cell metastasis. Using a systems biological computational method (shown in B), a drug target for the control of Rac2 was identified by our research team.  Inhibiting this target profoundly blocked cancer metastasis, suggesting a potential therapeutic application for this important discovery in patients.

The main point of this paper is that we have discovered a new mechanism that controls cancer cell metastasis and biomarkers which may allow us to test a specific tumor subtypes for evidence that this pathway is involved and hence, this represents a potential therapeutic target for the treatment of cancer metastasis. 

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Co-authors of the PLoS ONE manuscript include: Shweta Joshi, Alok Singh, Muamera Zulcic and Donald L. Durden were from the UCSD Department of Pediatrics; Karen Messer and Lei Bao were from the Department of Biostatistics; Janusz Dutkowski and Trey Ideker were from the UCSD, Institute for Systems Biology and Department of Medicine.

Funding for this study came from the National Institutes of Health grants RO1CA94233 and R21 HL093666 and the Hyundai Hope on Wheels, Hope grant.