Compounds and methods for modulating cell-adhesion mediated drug resistance
Peptides and methods of their use for inhibiting drug and radiation-therapy resistance in cancerous cells in which efficacy of chemotherapy and/or radiotherapy of a patient is enhanced by administration of an effective amount of a peptide that inhibits cell adhesion mediated drug resistance (CAM-DR). Preferably, the peptide comprises D-amino acids having the sequence: kmviywkag (RZ-3) or is a variant or modified version thereof. The peptide is preferably administered to the patient prior to chemotherapy and/or radiation therapy. Inhibition of cell adhesion mediated drug resistance (CAM-DR) by RZ-3 in multiple myeloma cells is disclosed.
1 . A method for inhibiting cell adhesion mediated drug resistance in a patient in need thereof, comprising:
administering to said patient an effective amount of a peptide that inhibits cell adhesion mediated drug resistance.
2 . The method of claim 1 , wherein said peptide comprises at least one D-amino acid.
3 . The method of claim 1 , wherein said peptide comprises the amino acid sequence:
kmviywkag
or a variant thereof.
4 . The method of claim 2 , wherein said peptide comprises RZ-3.
5 . The method of claim 4 , wherein said peptide is RZ-3.
6 . A method for enhancing the efficacy of chemotherapy or radiation therapy in a patient in need thereof, comprising:
administering an effective amount of a peptide, wherein said peptide inhibits cell adhesion mediated drug resistance in said patient; and
administering to said patient chemotherapy, radiation therapy, or both;
whereby the efficacy of said therapy is enhanced.
7 . The method of claim 6 , wherein said peptide comprises at least one D-amino acid.
8 . The method of claim 6 , wherein said peptide comprises the amino acid sequence:
kmviywkag
or a variant thereof.
9 . The method of claim 7 , wherein said peptide comprises RZ-3.
10 . The method of claim 9 , wherein said peptide is RZ-3.
11 . A method for treating cancer in a patient in need thereof, comprising:
administering to said patient an effective amount of a peptide, wherein said peptide inhibits cell adhesion mediated drug resistance in said patient; and
administering chemotherapy, radiation therapy or both.
12 . The method of claim 1 1 , wherein said peptide comprises at least one D-amino acid.
13 . The method of claim 11 , wherein said peptide comprises the amino acid sequence:
kmviywkag
or a variant thereof.
14 . The method of claim 12 , wherein said peptide comprises RZ-3.
15 . The method of claim 14 , wherein said peptide is RZ-3.
16 . The method of claim 1 1 , wherein said cancer is a myeloma.
17 . The method of claim 1 1 , wherein said cancer is multiple myeloma.
18 . A peptide comprising D-amino acids and having a sequence:
kmviywkag
or a variant thereof.
19 . A pharmaceutical composition comprising the peptide RZ-3, or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier.