Probing the CXCR6/CXCL16 Axis: Targeting Prevention of Prostate Cancer Metastasis

Information

  • Research Project
  • 8209517
  • ApplicationId
    8209517
  • Core Project Number
    R03MH095589
  • Full Project Number
    1R03MH095589-01
  • Serial Number
    95589
  • FOA Number
    PAR-09-129
  • Sub Project Id
  • Project Start Date
    9/9/2011 - 12 years ago
  • Project End Date
    8/31/2013 - 10 years ago
  • Program Officer Name
    YAO, YONG
  • Budget Start Date
    9/9/2011 - 12 years ago
  • Budget End Date
    8/31/2012 - 11 years ago
  • Fiscal Year
    2011
  • Support Year
    1
  • Suffix
  • Award Notice Date
    9/8/2011 - 12 years ago

Probing the CXCR6/CXCL16 Axis: Targeting Prevention of Prostate Cancer Metastasis

DESCRIPTION (provided by applicant): We have recently generated experimental data that validates the CXCR6/CXCL16 axis as a prostate cancer (PCa) therapeutic target. PCa is the second leading cause of cancer death in American men and its morbidity has increased globally in recent years. The high mortality rate is closely associated with the spread of malignant cells to various tissues including bone. Nearly 10% of patients whose conditions are diagnosed as PCa initially present with bone metastasis and almost all patients who die of prostate cancers have skeletal involvement. Identifying new mechanisms that control bone metastasis is of great consequence to facilitate the design of therapeutics aimed at decreasing metastatic risk and/or its complications. To address this unmet medical need, our team is actively engaged in exploring the chemical biology, medicinal chemistry, and therapeutic significance of modulating tumor cell trafficking and metastasis via chemokine receptor inhibition. This R03 application describes an MLPCN HTS-ready research program which is within the interests and expertise of our laboratories. The primary objective of this proposal is to use high throughput screening methods to identify small molecule antagonist probes that selectively inhibit CXCR6. Our team intends to address a key hypothesis: The CXCR6/CXCL16 axis significantly contributes to PCa cell metastasis and subsequent bone invasion. A small molecule antagonist would block cancer cell trafficking;hence mediate a metastatic event and disease progression to bone. We demonstrate supporting data that validates the role of the CXCR6/CXCL16 axis in PCa tumor progression, invasion, and proliferation. Thus, access to pharmacologically available small molecule antagonists will ultimately enable our studies in disease relevant models and allow for a more seamless translational advance to clinical applications. PUBLIC HEALTH RELEVANCE: Prostate cancer (PCa) is the second leading cause of cancer death in American men and its morbidity has increased globally in recent years. The high mortality rate is closely associated with the spread of malignant cells to various tissues including bone. Nearly 10% of patients whose conditions are diagnosed as PCa initially present with bone metastasis and almost all patients who die of prostate cancers have secondary skeletal tumor involvement. We are targeting the discovery of novel chemical probe molecules that block the signaling pathways driven by the CXCR6 receptor through receptor antagonism. This ultimately has utility as a potential therapeutic means to halt PCa disease progression and subsequent bone invasion.

IC Name
NATIONAL INSTITUTE OF MENTAL HEALTH
  • Activity
    R03
  • Administering IC
    MH
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    58350
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    310
  • Ed Inst. Type
  • Funding ICs
    OD:58350\
  • Funding Mechanism
    Research Projects
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    SANFORD-BURNHAM MEDICAL RESEARCH INSTIT
  • Organization Department
  • Organization DUNS
    020520466
  • Organization City
    LA JOLLA
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    920371005
  • Organization District
    UNITED STATES