A bacterial toxin that cleaves Ras: a translational study to provide insights into breast cancer biology and treatment

Project: Research project

Description

About 1/3 of all human cancers are driven by mutations in the
Rat sarcoma (RAS) genes. When RAS genes are mutated or Ras signaling is hyperactivated, cells
grow uncontrollably and evade death signals leading to cancer cell survival, tumor growth and invasive
cell behavior. Although only approximately 2% of breast cancers carry a RAS mutation, high Ras
activity has been detected in about 50% of breast cancer cell lines and tumor specimens. Despite
intensive exploration in the academic and private sector, no effective therapy that targets Ras or
hyperactive Ras currently exists and Ras is still considered as a virtually undruggable target for
therapy. We discovered that the Ras-Rap1-specific protease or RRSP from bacterium Vibrio vulnificus
has specific proteolytic activity against Ras and Rap1 small
GTPases, thus inhibiting proliferation of Ras-dependent and
Ras-independent cancer cell lines. Here we propose to test the
efficacy of RRSP in an in vivo xenograft mouse model of triplenegative
breast cancer. Our ultimate goal is to advance the
development of effective therapeutics for what is considered
one of the most undruggable targets in cancer research and
provide proof-of-principle pre-clinical evidence that RRSP can
block triple-negative breast cancer tumor growth.
StatusActive
Effective start/end date9/1/188/31/19

Funding

  • Northwestern Memorial Hospital (NMH Agmt #15 Exhibit B.10)

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Bacterial Toxins
Neoplasms
Breast Neoplasms
Triple Negative Breast Neoplasms
Mutation
Vibrio
Private Sector
Growth
Tumor Cell Line
Heterografts
Sarcoma
Genes
Cell Survival
Peptide Hydrolases
Bacteria
Cell Line
Therapeutics
Research