Resistance sequences and uses thereof
AssigneeMillennium Pharmaceuticals, Inc.
InventorShengfang Jin
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Abstract
Increased expression of resistance sequences is associated with drug resistance of certain cells (e.g., cancer cells). The invention provides methods for identifying drug resistant cells by measuring the expression or activity of resistance genes (e.g., semaphorin D, B94, mel-14 antigen, 24p3, proliferin, or maspin), methods for identifying modulators of drug resistance, and methods for modulating drug resistance by modulating the expression or activity of resistance sequences.
Claims22
A method for determining whether a test compound modulates the drug resistance of a cell, the method comprising:
- a) determining the level of expression or activity of a resistance sequence in a cell in the presence of a test compound;
- b) determining the level of expression or activity of the resistance sequence in the cell in the absence of the test compound;
- and
- c) identifying the compound as a modulator of drug resistance of the cell if the level of expression or activity of the resistance sequence in the cell in the presence of the test compound differs from the level of expression of the resistance sequence in the cell in the absence of the test compound.
A method for determining whether a test cell has a drug-resistant phenotype, the method comprising:
- a) measuring the expression or activity of a resistance sequence in the test cell;
- b) comparing the expression or activity of the resistance sequence measured in step a) to the expression or activity of the resistance sequence in a control cell not having a drug-resistant phenotype;
- and
- c) determining that the test cell has a drug resistant phenotype if the expression or activity of the resistance sequence in the test cell differs compared to the expression or activity of the resistance sequence in the control cell.
A method for determining whether a subject has or is at risk of developing a drug resistant tumor, the method comprising:
- a) measuring the expression of an up-regulated or down-regulated resistance mRNA in a biological sample comprising tumor cells obtained from the subject;
- b) comparing the expression of the mRNA measured in step a) to the expression of the mRNA in a control biological sample that is not drug resistant;
- and
- c) determining that the patient has or is at risk of developing a drug resistant tumor if the expression of an up-regulated mRNA in the biological sample obtained from the patient is higher than the expression of the up-regulated mRNA in the control biological sample, or decreased expression of a down-regulated mRNA in the biological sample obtained from the patient is lower than the expression of the down-regulated mRNA in the control biological sample.
A method for treating a drug resistant tumor in a patient, the method comprising administering to said subject an amount of an up-regulated protein antagonist or a down-regulated protein agonist effective to reduce drug resistance of said tumor in the patient.
A method for determining whether a drug therapy should be continued in a patient, the method comprising:
- a. obtaining a biological sample comprising tumor cells from the patient;
- b. determining the expression level of a resistance sequence in the patient sample;
- c. comparing the expression level determined in step (b) with the expression of the resistance sequence in a drug sensitive biological sample;
- and
- d. discontinuing treatment when the expression level of the resistance sequence in the patient sample is altered compared to the expression of the resistance sequence in the drug sensitive sample.
A method for determining whether a drug therapy should be continued in a patient, the method comprising
- a. obtaining a first patient biological sample comprising tumor cells and a second biological sample comprising tumor cells, wherein the first sample is obtained prior to the second sample;
- b. determining the expression level of a resistance sequence in the second sample;
- c. determining the expression level of a resistance sequence in the first sample;
- c. comparing the expression level of the resistance sequence determined in step (b) to the expression level of the resistance sequence in step (c);
- and
- d. discontinuing treatment when the expression level of the second sample differs from the expression level of the resistance sequence in the first sample.
A method for treating a drug resistant tumor in a patient, the method comprising administering to the patient a compound that reduces the expression of a protein selected from the group consisting of:
- semaphorin D, B94, mel-14 antigen, 24p3, and proliferin.
A method for treating a drug resistant tumor in a patient, the method comprising administering to the patient a compound that reduces the activity of a protein selected from the group consisting of:
- semaphorin D, B94, mel-14 antigen, 24p3, and proliferin.
A method for treating a drug resistant tumor in a patient, the method comprising administering to the patient a compound that increases the expression of maspin.
A method for treating a drug resistant tumor in a patient, the method comprising administering to the patient a compound that increases the activity of maspin.
A method for determining whether a drug therapy should be continued in a patient, the method comprising
- a. obtaining a first patient biological sample comprising tumor cells and a second biological sample comprising tumor cells, wherein the first sample is obtained prior to the second sample;
- b. determining the expression level of a gene selected from the group consisting of:
- semaphorin D, B94, mel-14 antigen, 24p3, and proliferin in the second sample;
- c. determining the expression level of the selected gene in the first sample;
- c. comparing the expression level determined in step (b) to the expression level determined in step (c);
- and
- d. discontinuing treatment when the expression level determined in step (b) is greater than the expression level determined in step (c).
A method for determining whether a drug therapy should be continued in a patient, the method comprising
- a. obtaining a first patient biological sample comprising tumor cells and a second biological sample comprising tumor cells, wherein the first sample is obtained prior to the second sample;
- b. determining the expression level of maspin in the second sample;
- c. determining the expression level of maspin in the first sample;
- c. comparing the expression level determined in step (b) to the expression level determined in step (c);
- and
- d. discontinuing treatment when the expression level determined in step (b) is less than the expression level determined in step (c).
Dependencies are inferred from the claim text.