Novel peptide inhibitors that disrupts the functional interactions of oncogenic protein PELP1 have been discovered by researchers at UT Health San Antonio. These inhibitors can be used for treatment of cancers that are characterized as over-expressing PELP1.
Background:
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 survival, development of hormonal therapy resistance, and metastasis. Targeting PELP1, an important downstream co-regulator molecule for many signaling pathways, could be more effective than other approaches that target upstream receptors or kinases . 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, these new 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 PIPs are extremely efficient in reducing the proliferation of ER-positive breast cancer cells, possibly by blocking oncogenic PELP1 and ER interactions which results in ER signaling interference. 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.
Commercial Applications and Advantages:
These novel peptides are applicable to the treatment of hormone related cancers that over express PELP1 and provides the following benefits over the current standard of care:
- Inhibit PELP1's interaction with epigenetic complexes and other proteins
- Reduce proliferation of ER+ and therapy resistant breast cancer cells
- Reduce stemness of Cancer Stem Cells and could prevent cancer recurrence
- Increased efficacy
- Use in other cancers that over-express PELP1 such as ovarian cancer and glioma