Methods and Composition for Inhibiting Proto-Oncogene PELP1

Tech ID:
HSC-1254
Description:

UT Health Science Center San Antonio (UTHSCSA) scientists have discovered novel peptide inhibitors that disrupt the functional interactions of an oncogenic protein, PELP1, for the treatment of cancers that overexpress this protein. 

 

PELP1 overexpression, noted in many hormone-related cancers such as breast, prostate, ovary and glioma, promotes cancer cell proliferation and is prognostically linked to shorter breast cancer specific survival, development of hormonal therapy resistance, and metastasis. PELP1 functions as a scaffolding protein by coupling various epigenetic signaling complexes to nuclear receptors, such as estrogen receptor (ER). Targeting PELP1, an important downstream co-regulator molecule for many signaling pathways, could be more effective than other approaches, targeting upstream receptors or kinases may cause resistance through ligand-independent constitutive activation or through the activation of alternate pathways. Recent evidence suggests that targeting protein interactions of PELP1 could be vital to inhibit the progression of these cancers.

 

While a majority of the drugs currently available target enzymatic activity or block ligand interaction with receptor molecules, the UTHSCSA peptide inhibitors represent a novel line of therapeutics that may make it possible to target protein-protein interaction and expand the number of functional targets in a cell. The novel, high affinity peptide inhibitors of PELP1 (PIPs) disrupt the functional interaction of this oncogenic protein. The peptides were further modified using a stapling technology that allows cell entry, provides resistance to proteases and enhances efficacy.

 

The PIPs were extremely efficient in reducing the proliferation of ER-positive breast cancer cells. Mechanism based studies suggest that PIPs block ER signaling by interfering with PELP1 mediated oncogenic interactions of ER with epigenetic modifiers. In therapy resistant breast cancer, this oncogenic interaction is sustained independent of estrogen, hence hormonal therapy is not effective. However, PIPs dramatically reduced the survival of therapy resistant breast cancer cells. PIPs also reduced the growth of breast cancer stem cells (CSCs) which suggests that PIPs could prevent cancer recurrence. The PIPs also included inhibitors that were effective in ER negative breast cancers, indicating that other oncogenic functions of PELP1 could be targeted using these PIPs.

 

Benefits and Advantages:

·        Novel peptide inhibitors of PELP1's interaction with epigenetic complexes and other proteins

·        PIPs reduce proliferation of ER+ and therapy resistant breast cancer cells

·        PIPs reduce stemness of Cancer Stem Cells and could prevent cancer recurrence

·        Modified PIP (sPIP) has increased efficacy

·        PIPs could be used in other cancers that overexpress PELP1 such as  ovarian cancer and glioma                                            

 

IP Status:                        Patent Pending                                                                                                                           

                                        Available for exclusive licensing; collaboration; development

Patent Information:
Category(s):
Therapeutics
For information contact:
John Fritz
Sr. Business Development Manager
Office of Technology Commercialization
FRITZJA@UTHSCSA.EDU
Inventors:
Ratna Vadlamudi
Monica Mann
Samaya Krishnan
Gangadhara Sareddy
Keywords: