Molecular subtyping, prognosis and treatment of prostate cancer

Patent metadata

Field	Value
Publication number	US-9568483-B2
Application number	US-201214112358-A
Country	US
Kind code	B2
Filing date	Mar 28, 2012
Priority date	Apr 18, 2011
Publication date	Feb 14, 2017
Grant date	Feb 14, 2017

Abstract

Disclosed herein are new prognostic molecular markers for prostate cancer. More specifically, the invention has identified that overexpression or amplification of at least one of AURKA or MYCN define a distinct subgroup of prostate cancer that is predisposed to the development of lethal NEPC, who will benefit from early intervention.

First claim

What is claimed is:

1. A method of subtyping prostate cancer, comprising:
obtaining a biological sample containing prostate cancer cells from a human subject having prostate cancer,
detecting amplification of AURKA in the biological sample by a fluorescent in situ hybridization (FISH) assay,
subtyping the prostate cancer as neuroendocrine prostate cancer (NEPC) or likely to develop into NEPC based on presence of the amplification of AURKA in the biological sample; and
administering a small molecule Aurora A kinase inhibitor to the human subject for treating prostate cancer subtyped as having NEPC or likely to develop NEPC.

2. The method of claim 1 , wherein said biological sample is a prostate tissue biopsy, urine, blood, semen, or prostatic secretions.

3. The method of claim 1 , further comprising detecting ERG rearrangement.

4. The method of claim 3 , wherein said ERG rearrangement is detected in a break-apart FISH assay.

5. The method of claim 1 , wherein said human subject has not been subjected to hormone therapy.

6. The method of claim 1 , wherein said human subject is undergoing hormone therapy.

7. The method of claim 1 , wherein said small molecule Aurora A kinase inhibitor is selected from the group consisting of VX-680/MK-0457, PHA-739358, MLN8054, MLN8237, SNS-314CYC116, PF-3814735, ENMD2076, AT-9283, R-763/AS-703569, and AMG900.

8. The method of claim 1 , wherein said amplification is determined based on a gain of at least one in the copy number of the AURKA gene.

9. The method of claim 8 , wherein said gain of at least one in the copy number of the AURKA gene is determined based on detecting at least three fluorescent signals in an interphase nucleus using a fluorescently labeled nucleic acid probe specific for the AURKA gene.

Assignees

• Rubin Mark A
• Beltran Himisha
• Univ Cornell

Inventors

• Rubin Mark A
• Beltran Himisha

Classifications

• G01N33/57555

  of the prostate · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• G01N33/6893 Primary

  related to diseases not provided for elsewhere · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title