Metastatic progression of the primary tumor accounts for the majority of cancer deaths. While the initial steps of the metastatic cascade are rather well defined, identification of targets to block this process remains a major clinical challenge. Previous studies have elegantly investigated the mechanistic contribution of tumor cell intrinsic properties that promote metastasis in bladder urothelial carcinomas. However, the functional significance of the tumor microenvironment and its contribution to this complicated process is not well characterized, and therefore, warrants investigation. The long-term goal of this renewal application is to continue explore how collagens?a major extracellular matrix component of the microenvironment?act as a ligand to mediate crosstalk with their receptor on tumor cells to facilitate the metastatic cascade. We will investigate the downstream regulatory mechanisms of collagen receptor signaling in both the primary tumor and metastatic sites, and to exploit these regulatory processes as a revolutionizing approach to target metastases. Such innovative approaches to perturb collagen-cancer crosstalk?not only at the primary tumor but also at the metastatic niche?will move the field forward by providing a new conception in metastatic disease management, and likely extend beyond bladder carcinomas to other cancer types.

Public Health Relevance

Metastatic bladder cancer is a devastating disease with a 5-year survival rate of only 5.4%. While the initial steps of the metastatic cascade are rather well defined, identification of targets to block this process continues to be a major clinical challenge. Discovering the regulatory mechanisms by which the metastatic microenvironment support tumor cell colonization and survival will enable design of new strategies not only targeting the primary tumors, but also eradicating metastatic foci ? a potential new breakthrough.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA175397-06A1
Application #
9972653
Study Section
Tumor Microenvironment Study Section (TME)
Program Officer
Snyderwine, Elizabeth G
Project Start
2013-09-30
Project End
2025-04-30
Budget Start
2020-05-15
Budget End
2021-04-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Cedars-Sinai Medical Center
Department
Type
DUNS #
075307785
City
Los Angeles
State
CA
Country
United States
Zip Code
90048
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