Exosome Associated Long Non-coding RNA Markers as Circulatory Cancer Biomarkers
Patent Number: Pending
Executive Summary:
General Description:
Triple-negative breast cancer (TNBC) does not express conventional therapeutic targets and is the only type of malignant breast cancer for which no designated FDA-approved targeted therapy is available. The inventors reported (ref. 1) that co-treatment with clinically validated inhibitors of c-ABL (imatinib) and EGFR (lapatinib) results in synergistic growth inhibition in TNBC cells. The dual treatment leads to synergistic repression of the long non-coding RNA HOTAIR (HOX Antisense Intergenic RNA). HOTAIR has been known to induce tumor growth and metastasis in breast cancer. Depleting HOTAIR alone phenocopies the dual treatment in growth suppression. Upregulation of HOTAIR is associated with TNBC in cell lines and a cohort of primary tumors.
This invention focuses on HOTAIR RNA associated with exosomes, naturally occurring lipid nanoparticles, which shed from all types of cells in the body, carrying parts of cytoplasm inside, and get into the bloodstream. The inventors discovered that the exosome-associated HOTAIR is a prognostic marker associated with TNBC and/or advanced breast cancer, such as tumors developing resistance to anti-estrogens. This non-invasive circulatory biomarker is expected to have a wide application in the management of breast cancer. Two target markets have been identified as relevant, including the oncology biomarker market and the HER2-negative breast cancer therapy market. Breast cancer is the most frequently diagnosed cancer in women worldwide, accounting for 25% of all new cancer cases in women. In 2012, nearly 1.7 million new cases of breast cancer were diagnosed. TNBC occurs in about 10% to 20% of diagnosed breast cancers.
Future Directions:
Strengths:
Weaknesses:
Publications:
Inventor Bio: Shao-Chun Wang
http://research.uc.edu/expertprofile.aspx?epersonID=wangsc
Executive Summary:
- Invention Type: Prognostic
- Patent Status: Application pending
- Patent Link: http://commercialization.uc.edu/business-industry/technology/ArticleID/115075/UCTechnologies/
- Research Institute: University of Cincinnati
- Disease Focus: Cancer
- Basis of Invention: Long non-coding RNA HOTAIR is found in the bloodstream of patients with advanced and/or triple-negative breast cancer (TNBC)
- How it works: HOTAIR levels can be detected quantitatively and with high sensitivity in patient blood samples using amplification by polymerase chain reaction
- Lead Challenge Inventor: Shao-Chun Wang
- Inventors: Shao-Chun Wang
- Development Stage: Pre-clinical
- Novelty:
- Application of HOTAIR non-coding long RNA as a biomarker in breast cancer and in response to targeted cancer treatment
- Isolation of HOTAIR from exosomes for prognostic purposes
- Clinical Applications:
- Evaluate the prognosis of TNBC or anti-estrogen-resistant breast cancers
- Determine the therapeutic responsiveness of breast cancers to dual treatment by imatinib and lapatinib
General Description:
Triple-negative breast cancer (TNBC) does not express conventional therapeutic targets and is the only type of malignant breast cancer for which no designated FDA-approved targeted therapy is available. The inventors reported (ref. 1) that co-treatment with clinically validated inhibitors of c-ABL (imatinib) and EGFR (lapatinib) results in synergistic growth inhibition in TNBC cells. The dual treatment leads to synergistic repression of the long non-coding RNA HOTAIR (HOX Antisense Intergenic RNA). HOTAIR has been known to induce tumor growth and metastasis in breast cancer. Depleting HOTAIR alone phenocopies the dual treatment in growth suppression. Upregulation of HOTAIR is associated with TNBC in cell lines and a cohort of primary tumors.
This invention focuses on HOTAIR RNA associated with exosomes, naturally occurring lipid nanoparticles, which shed from all types of cells in the body, carrying parts of cytoplasm inside, and get into the bloodstream. The inventors discovered that the exosome-associated HOTAIR is a prognostic marker associated with TNBC and/or advanced breast cancer, such as tumors developing resistance to anti-estrogens. This non-invasive circulatory biomarker is expected to have a wide application in the management of breast cancer. Two target markets have been identified as relevant, including the oncology biomarker market and the HER2-negative breast cancer therapy market. Breast cancer is the most frequently diagnosed cancer in women worldwide, accounting for 25% of all new cancer cases in women. In 2012, nearly 1.7 million new cases of breast cancer were diagnosed. TNBC occurs in about 10% to 20% of diagnosed breast cancers.
Future Directions:
- Clinical validation of prognostic accuracy
Strengths:
- Highly sensitive, relatively inexpensive prognostic technique
Weaknesses:
- The technology is at an early stage of the development
- Relevant publications are not yet available
Publications:
- Wang YL, Overstreet AM, Chen MS, Wang J, Zhao HJ, Ho PC, Smith M, Wang SC. Combined inhibition of EGFR and c-ABL suppresses the growth of triple-negative breast cancer growth through inhibition of HOTAIR. Oncotarget. 2015 May 10;6(13):11150-61. PubMed PMID: 25883211; PubMed Central PMCID: PMC4484446.
Inventor Bio: Shao-Chun Wang
http://research.uc.edu/expertprofile.aspx?epersonID=wangsc