Compounds and methods for modulating cell-adhesion mediated drug resistance

A method for enhancing the efficacy of chemotherapy or radiation therapy in a patient in need thereof, comprising:

• administering to the patient an effective amount of a peptide comprising the amino acid sequence Lys-Met-Val-Ile-Tyr-Trp-Lys-Ala-Gly (SEQ ID NO:5), or a pharmaceutically acceptable salt thereof, wherein the peptide inhibits cell adhesion mediated drug resistance in the patient;
• and
• administering chemotherapy, radiation therapy, or both, to the patient;
• whereby the efficacy of the chemotherapy, radiation therapy, or both, is enhanced.

A method for inhibiting cell adhesion mediated drug resistance in a patient in need thereof, comprising:

• administering to the patient an effective amount of a peptide that inhibits cell adhesion mediated drug resistance, wherein the peptide comprises the amino acid sequence Lys-Met-Val-Ile-Tyr-Trp-Lys-Ala-Gly (SEQ ID NO:5), or a pharmaceutically acceptable salt or variant thereof, wherein the variant has at least one of the following modifications:
• the variant contains one or more hydroxyproline or hydroxylysine;
• the variant contains an organic acid or amide;
• the variant contains a C-terminal carboxylate;
• the variant is esterified;
• the variant is amidated;
• the variant has a modified N-terminal amino group;
• the variant has a side-chain modification or substitution selected from the group consisting of methylation, benzylation, t-butylation, tosylation, and alcoxycarbonylation;
• the variant has an N-acetyl group;
• the variant has a C-terminal amide group;
• or the variant has an amino acid selected from the group consisting of penicillamine, tetramethylene cysteine, pentamethylene cysteine, mercaptopropionic acid, pentamethylene-mercaptopropionic acid, 2-mercaptobenzene, 2-mercaptoaniline, 2-mercaptoproline, ornithine, diaminobutyric acid, aminoapidic acid, m-aminomethylbenzoic acid, and diaminopropionic acid.

A method for enhancing the efficacy of chemotherapy or radiation therapy in a patient in need thereof, comprising:

• administering to the patient an effective amount of a peptide comprising the amino acid sequence Lys-Met-Val-Ile-Tyr-Trp-Lys-Ala-Gly (SEQ ID NO:5), or a pharmaceutically acceptable salt or variant thereof, wherein the peptide inhibits cell adhesion mediated drug resistance in the patient, and wherein the variant has at least one of the following modifications:
• the variant contains one or more hydroxyproline or hydroxylysine;
• the variant contains an organic acid or amide;
• the variant contains a C-terminal carboxylate;
• the variant is esterified;
• the variant is amidated;
• the variant has a modified N-terminal amino group;
• the variant has a side-chain modification or substitution selected from the group consisting of methylation, benzylation, t-butylation, tosylation, and alcoxycarbonylation;
• the variant has an N-acetyl group;
• the variant has a C-terminal amide group;
• or the variant has an amino acid selected from the group consisting of penicillamine, tetramethylene cysteine, pentamethylene cysteine, mercaptopropionic acid, pentamethylene-mercaptopropionic acid, 2-mercaptobenzene, 2-mercaptoaniline, 2-mercaptoproline, ornithine, diaminobutyric acid, aminoapidic acid, m-aminomethylbenzoic acid, and diaminopropionic acid;
• and
• administering chemotherapy, radiation therapy, or both, to the patient, whereby the efficacy of the chemotherapy, radiation therapy, or both, is enhanced.

A method for treating cancer in a patient in need thereof comprising:

• administering to the patient an effective amount of a peptide comprising the amino acid sequence Lys-Met-Val-Ile-Tyr-Trp-Lys-Ala-Gly (SEQ ID NO:5), or a pharmaceutically acceptable salt or variant thereof, wherein the peptide inhibits cell adhesion mediated drug resistance in the patient, and wherein the variant has at least one of the following modifications:
• the variant contains one or more hydroxyproline or hydroxylysine;
• the variant contains an organic acid or amide;
• the variant contains a C-terminal carboxylate;
• the variant is esterified;
• the variant is amidated;
• the variant has a modified N-terminal amino group;
• the variant has a side-chain modification or substitution selected from the group consisting of methylation, benzylation, t-butylation, tosylation, and alcoxycarbonylation;
• the variant has an N-acetyl group;
• the variant has a C-terminal amide group;
• or the variant has an amino acid selected from the group consisting of penicillamine, tetramethylene cysteine, pentamethylene cysteine, mercaptopropionic acid, pentamethylene-mercaptopropionic acid, 2-mercaptobenzene, 2-mercaptoaniline, 2-mercaptoproline, ornithine, diaminobutyric acid, aminoapidic acid, m-aminomethylbenzoic acid, and diaminopropionic acid;
• and
• administering chemotherapy, radiation therapy, or both, to the patient.