Biomarkers for Assessing Peripheral Neuropathy Response to Cancer Treatment

• US 20100249065A1
• Filed: 03/24/2010
• Published: 09/30/2010
• Est. Priority Date: 03/24/2009
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Sun, Yu, Favis, Reyna, Cohen, Nadine, Li, Qingqin, Ricci, Deborah, van de Velde, Helgi
• Granted Patent: US 9,605,317 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

The present invention provides methods for identifying patients at increased risk of developing an adverse neurological event in response to a cancer treatment. Methods also include modifying the treatment regimen of said patent dependent on the presence or absence of biomarkers in the patient.

Claims

1. A method for identifying whether a patient is at increased risk for developing an adverse neurological event in respond to a cancer treatment, comprising:

determining whether or not said patient possesses one or more biomarkers for said increased risk, wherein the presence of said biomarker indicates an increased risk for said adverse neurological event.

2. The method of claim 1, wherein said adverse neurological event is selected from the group consisting of peripheral neuropathy, peripheral sensory neuropathy and neuralgia.

3. The method of claims 1-2, wherein said cancer treatment comprises administration of a proteosome inhibitor.

4. The method of claim 3, wherein said proteosome inhibitor comprises bortezomib.

5. The method of claims 1-2, wherein said biomarker is selected from the group consisting of rs4553808;

rs1474642;

rs12568757;

rs11974610; and

rs126134.

6. The method of claim 4, wherein said biomarker is selected from the group consisting of rs4553808;

rs1474642;

rs12568757;

rs11974610; and

rs126134.

7. The method of claim 1, wherein said determining comprises obtaining a biological sample from said patient, and performing genotyping analysis on said sample.

8. A diagnostic kit or equivalent for identifying patients likely to develop an adverse event in response to treatment for cancer, comprising:

a biomarker selected from the group consisting of one or more of the sequence variances in the candidate genes listed in Appendix 1; and

instructions for employing said biomarker to identify patients likely to develop peripheral neuropathy in response to treatment for cancer.

9. A method for treating a patient for cancer comprising:

determining whether or not said patient possesses one or more biomarkers for increased risk of developing an adverse neurological event in response to a cancer treatment, wherein the presence of said biomarker indicates an increased risk for said adverse neurological event; and

selecting a first method of treatment or a second method of treatment, wherein said first method of treatment and second method of treatment are dependent on whether said patient is likely to develop peripheral neuropathy in response to said treatment for cancer.

10. The method of claim 9, wherein if said patient is determined not to be likely to develop peripheral neuropathy in response to said treatment for cancer, said first method of treatment is employed.

11. The method of claim 9, wherein if said patient is determined to be likely to develop peripheral neuropathy in response to said treatment for cancer, said second method of treatment is employed.

12. The method of claim 10, wherein said first method of treatment comprises treating said patient with an agent that provides a physiological effect directed against said cancer without modification for peripheral neuropathy.

13. The method of claim 11, wherein said second method of treatment comprises treating said patient with an agent that provides a physiological effect directed against said cancer with modification for peripheral neuropathy.

14. The method of claim 13, wherein said modification comprises reducing a dose of said agent.

15. The method of claim 13, wherein said modification comprises eliminating use of said agent.

16. The method of claim 13, wherein said modification comprises administering an agent known to treat peripheral neuropathy.

17. A method for selecting a patient for administration of a method of treatment for cancer, comprising:

comparing a presence or absence of at least one biomarker selected from the group consisting of one or more of the sequence variances in the candidate genes listed in Appendix 1 in cells of said patient with a list of variances, wherein the presence of at least one variance is indicative that said method of treatment for cancer may be deleterious to said patient, and modifying said method of treatment for cancer if said at least one variance is present in said patient'"'"'s cells.