Molecular diagnostic test for cancer

• US 9,677,140 B2
• Filed: 10/07/2013
• Issued: 06/13/2017
• Est. Priority Date: 09/15/2010
• Status: Active Grant

• Current Assignee: Almac Diagnostic Services Limited
• Original Assignee: Almac Diagnostics Limited
• Inventors: O'Donnell, Jude, Bylesjo, Max, Patterson, Fionnuala, Deharo, Steve, Hill, Laura A., Keating, Katherine E., Davison, Timothy, Proutski, Vitali, Harkin, Denis Paul, Kennedy, Richard, Goffard, Nicolas
• Primary Examiner(s): Zhang, Kaijiang
• Application Number:
  US14/047,949
• Publication Number:
  US 20140031260A1
• Time in Patent Office: 1,345 Days
• Field of Search: None
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: C12Q 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• 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 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/20 Supervised data analysis
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment

Abstract

Methods and compositions are provided for the identification of a molecular diagnostic test for cancer. The test defines a novel DNA damage repair deficient molecular subtype and enables classification of a patient within this subtype. The present invention can be used to determine whether patients with cancer are clinically responsive or non-responsive to a therapeutic regimen prior to administration of any chemotherapy. This test may be used in different cancer types and with different drugs that directly or indirectly affect DNA damage or repair, such as many of the standard cytotoxic chemotherapeutic drugs currently in use. In particular, the present invention is directed to the use of certain combinations of predictive markers, wherein the expression of the predictive markers correlates with responsiveness or non-responsiveness to a therapeutic regimen.

Claims

1. A method of treating a cancer patient with a DNA-damage therapeutic agent, comprising administering the DNA-damage therapeutic agent to the patient, wherein, prior to administration of the therapeutic agent, the patient has been determined to overexpress either (i) the combined level of the mRNAs for APOL3 and at least one of the other genes of Table 2B, (ii) the combined level of the mRNAs for IDO1 and at least one of the other genes of Table 2B, or (iii) the combined level of the mRNAs for CXCL10 and at least one of the other genes of Table 2B.

2. The method according to claim 1, wherein the cancer is chosen from melanoma, colon cancer, breast cancer, and ovarian cancer.

3. The method according to claim 2, wherein the cancer is breast cancer.

4. The method according to any one of claims 1-3, wherein the DNA-damage therapeutic agent comprises one or more substances selected from the group consisting of:

a DNA damaging agent, a DNA repair targeted therapy, an inhibitor of DNA damage signaling, an inhibitor of DNA damage induced cell cycle arrest, a histone deacetylase inhibitor, an inhibitor of DNA synthesis, and a heat shock protein inhibitor.

5. The method according to claim 4, wherein the DNA damaging agent comprises one or more of an anthracycline, a cisplatin, a carboplatin, a cyclophosphamide, an oxaliplatin, a busulphan, an irinotecan, a topotecan, an etoposide, a doxorubicin, an epirubicin, and ionising radiation.

6. The method according to claim 4, wherein the cancer is breast cancer and the DNA-damage therapeutic agent comprises a combination of a 5-fluorouracil, an anthracycline, and a cyclophosphamide.

7. The method according to claim 6, wherein the anthracycline is epirubicin.

8. The method according to claim 6, wherein the anthracyline is doxorubicin.

9. The method according to claim 6, wherein a taxane is co-administered with the DNA-damage therapeutic agent.

10. The method according to claim 4, wherein the cancer is ovarian cancer and the DNA-damage therapeutic agent comprises a platinum-containing agent.

11. The method according to claim 10, wherein DNA-damage therapeutic agent is co-administered with a taxane.

12. The method according to claim 1, wherein, prior to administration of the therapeutic agent, the patient has been determined to overexpress the combined level of the mRNAs for APOL3 and at least one of the other genes of Table 2B.

13. The method according to claim 1, wherein, prior to administration of the therapeutic agent, the patient has been determined to overexpress the combined level of the mRNAs for IDO1 and at least one of the other genes of Table 2B.

14. The method according to claim 1, wherein, prior to administration of the therapeutic agent, the patient has been determined to overexpress the combined level of the mRNAs for CXCL10 and at least one of the other genes of Table 2B.