WO 2008/106730 A1 - Methods For Detecting And Modulating The Sensitivity Of Tumour Cells To Anti-mitotic Agents - The Lens - Free & Open Patent and Scholarly Search

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WO 2008/106730 A1

Methods For Detecting And Modulating The Sensitivity Of Tumour Cells To Anti-mitotic Agents

Published: Sep 12, 2008
Earliest Priority: Mar 05 2007
Family: 20
Cited Works: 8
Cited by: 0
Cites: 1
Additional Info: Cited Works Full text Published

Abstract

A method of screening a tumour cell for resistance to a tubulin-binding agent, the method comprising detecting the expression of any one or more of class II, class III and class IVb ß-tubulin by the tumour cell, wherein the expression of any one or more of class II, class III and class IVb ß-tubulin indicates that the tumour cell has resistance or potential resistance to the tubulin-binding agent.

Claims

A method of screening a tumour cell for resistance to a tubulin-binding agent, the method comprising detecting the expression of any one or more of class II, class
III and class IVb β-tubulin by the tumour cell, wherein the expression of any one or more of class II, class HI and class IVb β-tubulin indicates that the tumour cell has resistance or potential resistance to the tubulin-binding agent.
The method according to claim 1 wherein detecting the expression of any one or more of class II, class III and class IVb β-tubulin by the tumour cell comprises detecting the expression of any two of class H, class III and class IVb β-tubulin by the tumour cell.
The method according to claim 1, wherein detecting the expression of any one or more of class II, class III and class IVb β-tubulin by the tumour cell comprises detecting the expression of class II, class III and class IVb β-tubulin by the tumour cell.
The method according to claim 1, wherein detecting the expression of one or more of class II, class III and class IVb β-tubulin by the tumour cell comprises detecting the expression of any one or more of class II, class III and class IVb β-tubulin protein by the tumour cell.
The method according to claim 1, wherein detecting the expression of any one or more of class II, class III and class IVb β-tubulin by the tumour cell comprises detecting the expression of any one or more of class II, class III and class IVb β- tubulin mRNA by the tumour cell. 6. The method according to claim 1 , wherein detecting the expression of one or more of class II, class III and class IVb β-tubulin by the tumour cell comprises quantifying the level of expression of any one or more of class II, class HI and class IVb β-tubulin by the tumour cell.
The method according to claim 1 , wherein detecting the expression of one or more of class II, class III and class IVb β-tubulin by the tumour cell comprises comparing the expression of one or more of class II, class III and class IVb β- tubulin by the tumour cell with the expression of one or more of class II, class III and class IVb β-tubulin by a control cell.
A method of assessing the resistance of a tumour cell to a tubulin-binding agent, the method comprising: detecting an amount of any one or more of class II, class III and class IVb β- tubulin protein or any one or more of class II, class III and class IVb β-tubulin mRNA by the tumour cell and thereby obtaining a subject tumour cell tubulin amount, comparing the subject tumour cell tubulin amount to a control cell tubulin amount thereby determining a tubulin amount difference, wherein the control cell tubulin amount is a respective amount of a class II, class III or class IVb β-tubulin protein or any one or more of class II, class III and class IVb β-tubulin mRNA in a control cell, and assessing resistance of the tumour cell to the tubulin-binding agent based on the tubulin amount difference.
The method according to claim 7 or claim 8, wherein the control cell is a control non tumour cell.
The method according to claim 7 or claim 8, wherein the control cell is a control tumour cell.
1 1. The method according to claim 10, wherein the control tumour cell is a tumour cell which is resistant to the tubulin-binding agent.
The method according to claim 10, wherein the control tumour cell is a tumour cell which is sensitive to the tubulin-binding agent. 13. The method according to claim 8, wherein detecting an amount of any one or more of class II, class III and class IVb β-tubulin protein is detecting an amount of class II, class III and class IVb β-tubulin protein.
The method according to claim 8, wherein detecting an amount of any one or more of class II, class III and class IVb β-tubulin protein is detecting an amount of class III β-tubulin protein only.
The method according to claim 9, wherein detecting an amount of any one or more of class II, class III and class IVb β-tubulin mRNA is detecting an amount of class II, class III and class IVb β-tubulin mRNA.
The method according to claim 9, wherein detecting an amount of any one or more of class II, class III and class IVb β-tubulin mRNA is detecting an amount of class
III β-tubulin mRNA only.
A method for enhancing the sensitivity of a tumour cell to a tubulin-binding agent, the method comprising introducing into the tumour cell an effective amount of at least one nucleic acid construct comprising a nucleotide sequence specific to at least a portion of the class II, class III or class IVb β-tubulin gene product, wherein the construct decreases the expression of class II, class III or class IVb β-tubulin in the tumour cell and thereby increases the sensitivity of the tumour to the tubulin- binding agent.
A method for treating a tumour cell in a subject, comprising administering to the s subject an effective amount of at least one nucleic acid construct comprising a nucleotide sequence specific to at least a portion of the class II, class HI or class IVb β-tubulin gene product and administering to the subject a tubulin-binding agent, wherein the nucleic acid construct decreases the expression of class II, class III or class IVb β-tubulin in the tumour and thereby increases the sensitivity of the o tumour cell to the tubulin-binding agent.
The method according to claim 17 or claim 18, wherein the nucleic acid construct and the tubulin-binding agent are administered simultaneously.
The method according to claim 17 or claim 18, wherein the nucleic acid construct and the tubulin-binding agent are administered concurrently. s 21. The method according to claim 17 or claim 18, wherein the nucleic acid construct is administered before the tubulin-binding agent. 22. The method according to claim 17 or claim 18 wherein the nucleotide sequence is selected from the group consisting of an antisense sequence, an siRNA sequence, a short hairpin RNA sequence and a ribozyme sequence. 0 23. The method according to claim 17 or claim 18, wherein the nucleotide sequence is specific to at least a portion of the class IVb β-tubulin gene product.
The method according to claim 17 or claim 18, wherein the nucleotide sequence is specific to at least a portion of the class II β-tubulin gene product.
The method according to claim 17 or claim 18, wherein the nucleotide sequence is 5 specific to at least a portion of the class III β-tubulin gene product.
The method according to any one of claims 1 to 25, wherein the tubulin-binding agent is a microtubule destabilizing agent.
The method according to claim 26, wherein the microtubule destabilizing agent is selected from the group consisting of any a vinca alkaloid, a dolostatin, a 0 colchicine, a cryptophycin, curacin A, and 2-methoxyestradiol.
The method according to any one of claims 1 to 25, wherein the tubulin-binding agent is a microtubule stabilizing agent.
The method according to claim 30, wherein the microtubule stabilizing agent is selected from the group consisting of a taxane and an epothilone.
The method according to any one of claims 1 to 29, wherein the tumour cell is a non-small cell lung carcinoma cell.
The method according to any one of claims 1 to 30, wherein the tumour cell is a human tumour cell. 32. The use of at least one nucleic acid construct comprising a nucleotide sequence specific to at least a portion of the class II, class III or class IVb β-tubulin gene product, wherein the construct is able to decrease the expression of class II, class III or class IVb β-tubulin in a tumour cell, in the preparation of a medicament for increasing the sensitivity of a tumour cell to a tubulin-binding agent. 33. A pharmaceutical composition for increasing the sensitivity of a tumour to a tubulin-binding agent, the pharmaceutical composition comprising at least one nucleic acid construct comprising a nucleotide sequence specific to at least a portion of the class II, class HI or class IVb β-tubulin gene, wherein the construct is able to decrease the expression of class II, class III or class IVb β-tubulin in a tumour, together with a pharmaceutically acceptable carrier, diluent or excipient.
A kit when used for assessing the sensitivity of a tumour to a tubulin-binding agent, the kit comprising at least one nucleic acid construct comprising a nucleotide sequence specific to at least a portion of the class II, class III or class IVb β-tubulin gene product, or at least one antibody specific to at least one of the class II, class III or class IVb β-tubulin protein, wherein the construct or antibody is used to detect the expression of class II, class IH or class IVb β-tubulin in the tumour.
The kit according to claim 34, further comprising a tubulin-binding agent.

Applicants

Newsouth Innovations Pty Ltd
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Kavallaris Maria
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Gan Pei Pei
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Inventors

Kavallaris Maria
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Gan Pei Pei
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CPC Classifications

A61K2300/00
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A61K31/165
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A61K31/7088
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A61K45/06
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A61K48/00
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C12N15/113
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C12N2310/111
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C12N2310/14
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C12N2310/53
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C12N2320/30
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C12Q1/6886
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C12Q2600/158
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G01N2800/44
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G01N2800/52
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G01N2800/56
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G01N33/5011
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G01N33/5044
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G01N33/57496
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IPC Classifications

A61K31/7088
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G01N33/483
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Document History

Publication: Sep 12, 2008
WO 2008/106730 A1
Application: Mar 5, 2008
AU 2008/000298 W
Priority: Sep 28, 2007
AU 2007/905307 A
Priority: Mar 5, 2007
AU 2007/901131 A