Novel malignancy associated response signatures associated with refractory tumors
Inventors: Judy Lieberman, Fabio Petrocca
Invention Types: Diagnostic/Prognostic, Therapeutics
Research Areas: Oncology/Hematology, Reproduction/Ob-Gyn
Keywords: Drug Screening, Stem/Progenitor CellFor More Information Contact: Ives, Catherine L.
Despite basic and clinical research directed at understanding and controlling breast cancer, breast cancer is still a major health threat worldwide. Triple-negative breast cancers (TNBC) are an especially aggressive group of tumors with the shortest survival of all breast cancer subtypes.
Dr. Lieberman's laboratory has found novel malignancy associated response signatures and assays and methods to classify and diagnose tumors, such as TNBC and other poor prognosis tumors, using a newly identified dependency gene signature associated with breast cancer malignancy (TGS). TGS expression correlates with poor survival and early onset of metastasis in breast cancer patients independent of tumor subtype. This technology is based on findings of a genome-wide siRNA lethality screen in human tumor-initiating epithelial cells, which initiate TNBC-like lesions in mice. Dr. Lieberman's laboratory identified core survival pathways and a malignancy associated response signature that are selectively associated with tumor-initiating potential that are useful for prognostic and diagnostic applications.
These efforts have uncovered new uses for drugs acting as proteasome inhibitors, Mcl-1 inhibitors, AKT inhibitors, histone deacetylase inhibitors, glycolysis inhibitors, or a combination thereof as well as novel therapeutic targets for more effective and enhanced treatment of poor prognosis tumors, such as TNBC.
These discoveries provide a platform by which companies can diagnose and treat TNBCs with novel and next generation drugs.
• Novel malignancy associated response signatures and assays and methods thereof to classify and diagnose tumors, such as TNBC and other poor prognosis breast tumors, using a newly identified dependency gene signature identified in TNBC-initiating cells.
• New uses of drugs acting as proteasome inhibitors, Mcl-1 inhibitors, AKT inhibitors, histone deacetylase inhibitors, glycolysis inhibitors, or a combination thereof.
• New methods to screen for novel drugs for treating cancers and tumors, such as TNBC.
• TNBC have the shortest survival of all breast cancer subgroups.
• TNBC rapidly acquire resistance to chemotherapy and are refractory to endocrine therapy and HER-2 inhibitors.
• This technology could diagnose deadly breast tumors early and increase the chance of a patient's survival.
• This technology could lead to new effective drugs to treat certain forms of deadly breast cancers.
Exclusive license available and/or sponsored research
Petrocca F, Altschuler G, Tan SM, et al. A genome-wide siRNA screen identifies proteasome addiction as a vulnerability of basal-like triple-negative breast cancer cells. Cancer Cell. 2013 Aug 12;24(2)
Chan S, Sridhar P, Kirchner R, et al. Basal-A triple-negative breast cancer cells selectively rely on RNA splicing for survival. Mol Cancer Ther. 2017 Dec;16(12)
IPStatus: Pat. Pend.