Targeting of PELP1 in cancer therapy
The disclosure describes PELP1 binding peptides and peptoids and their use the interaction of PELP1 with molecules that lead to oncogenic signaling in cancers.
1. A pharmaceutical composition comprising (a) a peptide or peptoid comprising a full-length sequence selected from SEQ ID NO: 1, 2, 3, 65, 66, 67, or 68 and is no more than 30 residues in length and (b) a pharmaceutically acceptable carrier, buffer or diluent.
2. The composition of claim 1 , wherein said peptide or peptoid is fused to a cell penetrating peptide.
3. The composition of claim 1 , wherein said peptide is a stapled peptide or comprises a bridge.
4. The composition of claim 3 , wherein said bridge comprises a linker, chemically modified side chains, or hydrocarbon stapling.
5. The composition of claim 4 , wherein the linker comprises a modification that stabilizes an alpha-helical structure of said peptide.
6. A method of inhibiting a cancer cell in a subject comprising administering to said subject a peptide or peptoid that binds to PELP1 and blocks one or more estrogen receptor co-activation functions of PELP1, wherein said peptide or peptoid comprises a full-length sequence selected from SEQ ID NO: 1, 2, 3, 65, 66, 67, or 68 and is no more than 30 residues in length.
7. The method of claim 6 , wherein the cancer cell is a prostate, breast, glioma or ovarian cancer cell.
8. The method of claim 6 , wherein said peptide or peptoid is fused to a cell penetrating peptide.
9. The method of claim 6 , wherein administering comprises intravenous, intra-arterial, intra-tumoral, subcutaneous, topical or intraperitoneal administration.
10. The method of claim 6 , wherein administering comprises local, regional, systemic, or continual administration.
11. The method of claim 6 , wherein inhibiting comprises inducing growth arrest of said tumor cell, apoptosis of said tumor cell and/or necrosis of a tumor tissue comprising said tumor cell.
12. The method of claim 6 , further comprising administering to said subject a second anti-cancer therapy.
13. The method of claim 6 , wherein said subject is a human.
14. The method of claim 6 , wherein said peptide or peptoid is administered at 0.1-500 mg/kg/d.
15. The method of claim 6 , wherein said estrogen receptor co-activator function comprises PELP1 binding to histone lysine methyltransferase G9a.