CARP-1/CCAR1 Functional Mimetics (CFMs): Novel small molecule suppressors of human breast cancer cell growth.

Case ID:
09-958

CARP-1/CCAR1 functional mimetics (CFMs): Novel small molecule suppressors of human breast cancer cell growth.  

WSU Tech#: 09-958

Technology Summary:

CARP-1 (Cell cycle and apoptosis regulator protein) is a regulator of cell growth signaling. CARP-1 plays an important role in apoptosis (cell death) induction in human breast cancer (HBC) cells in the presence of the chemotherapy agent Adriamycin. The researchers have found that CARP-1 inhibits cell growth by binding with the anaphase promoting complex (APC)-2 protein. Since breast cancers often have dysregulated cell cycle signaling, the researchers hypothesize that CARP-1 mimetics that target APC-2/cell cycle signaling will inhibit HBC cell survival pathways.

The researchers? work has shown that CARP-1 is a regulator of apoptosis, induced when proliferation signaling by epidermal growth factor receptor (EGFR) is inhibited. The EGFR family of proteins is a known risk factor for development of disease, predictors of prognosis and response to therapy, and is utilized as therapeutic targets against a variety of cancers including breast cancer. Small molecule CARP-1 mimetics have been generated and shown to facilitate effective targeting of key oncogenes (APC-2) and serve as efficacious anti-tumor agents for treatment of breast cancer alone or in conjunction with chemotherapy agents.

The researchers have developed 3 lead CARP-1 inhibitors, CFM-4, CFM 4.16 and CFM 4.17.  These have been tested and shown effective in vitro and in vivo against Triple Negative Breast Cancers (TNBC) and lung cancer (including an in vivo metastatic model).  PK data is also available for these therapeutics.

Benefit Analysis:

 

The market for Breast cancer drugs reached $12.7 billion in 2010 and came down to $10.2 billion in 2011, likely due to many drugs going generic.  The market is expected to reach $11.2 billion by 2016, a CAGR of 1.9%. The Majority of the breast cancers are ER-positive and treated by conventional anti-estrogens in combination with inhibitors of estrogen synthesis.  The ER-negative, HER2-positive tumors are treated with Herceptin- HER-2 targeting antibodies. 

Triple-negative breast cancers (TNBCs; ER/PR/HER-2-negative) are treated with chemo (Doxorubicin/Adriamycin; ADR) in combination with radiation and surgery.   TNBCs represent approximately 15% of all breast cancers (~31,500 in the US).  It has been found that African Americans are three times more likely to have TNBC than other ethnic groups and that 39% of all breast cancers in premenopausal African American women are TNBC. In 2009, ~106 new breast cancer therapies were in development.  Most therapies target growth survival signaling (EGFR, HER2, VEGF, Ras, proteasome) or activate apoptosis signaling (p53, TRAIL receptors).  This technology provides a new target intervention strategy using small molecules with demonstrated in vivo activity and are the only drugs known for the novel CARP-1 targets.  These small molecules are readily synthesized using standard chemistry techniques and easily scalable for mass production.

Stage of Development: Available

 

Patent Status:

 

US, European and Canadian patent applications submitted.

 

Licensing Opportunity:

WSU is looking for commercial partners interested in furthering the validation of this technology and bringing the technology to market.  The inventors would be open to assist in the generation of SBIR/STTR grants to fund the further development of this technology.

Contact for Further Information:  

 Frank Urban, MS, CBA, BA.   email: frank.urban@wayne.edu   Phone (mobile): (734) 355-0730

Patent Information:
For Information, Contact:
Frank Urban
Commercialization Principal
Wayne State University
frank.urban@wayne.edu
Inventors:
Arun Rishi
Keywords: