Genetic variations associated with drug resistance

Patent metadata

Field	Value
Publication number	US-11021711-B2
Application number	US-201715838042-A
Country	US
Kind code	B2
Filing date	Dec 11, 2017
Priority date	Mar 14, 2008
Publication date	Jun 1, 2021
Grant date	Jun 1, 2021

Abstract

Methods and compositions are provided to determine if a cancer is resistant to treatment with anti-mitotic agents, including treatment with T-DM1. The methods relate to determining if the ABCC3 gene is amplified and/or overexpressed in the cancer.

First claim

What is claimed is:

1. A method for selecting a human patient with HER2-positive breast cancer for treatment with an anti-mitotic chemotherapy agent comprising:
a) selecting the human patient with HER2-positive breast cancer by determining in a tumor tissue sample obtained from the human patient with HER2-positive breast cancer, (i) a copy number of an ABCC3 gene in the tumor tissue sample of less than 3 or (ii) an ABCC3 gene amplification value in the tumor tissue sample of less than 1.8 relative to an amplification value of a centromere 17 (CEP17) gene in the tumor tissue sample, and
b) treating the selected human patient with HER2-positive breast cancer by administering an effective amount of an anti-mitotic chemotherapy agent,
wherein the anti-mitotic chemotherapy agent is selected from the group consisting of taxanes, maytansinoids, auristatins and analogs and derivatives thereof.

2. The method of claim 1 , wherein the copy number of the ABCC3 gene is determined by fluorescence in situ hybridization (FISH), Southern Blot, immunohistochemisty (IHC), polymerase chain reaction (PCR), quantitative PCR (qPCR), quantitative real-time PCR (qRT-PCR), comparative genomic hybridization, microarray based comparative genomic hybridization, or ligase chain reaction (LCR).

3. The method of claim 1 , wherein the taxane is selected from the group consisting of paclitaxel and docetaxel.

4. The method of claim 1 , wherein the auristatin is selected from the group consisting of monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF).

5. The method of claim 1 , wherein the maytansinoid is selected from the group consisting of DM1 and DM4.

6. The method of claim 1 , wherein the anti-mitotic chemotherapy agent is conjugated to an antibody.

7. The method of claim 6 , wherein the anti-mitotic chemotherapy agent-antibody conjugate is a maytansinoid-anti-Her2 antibody conjugate.

8. The method of claim 7 , wherein the maytansinoid-anti-Her2 antibody conjugate is trastuzumab-DM1.

Assignees

• Genentech Inc

Inventors

• Lackner Mark
• Amler Lukas C
• Cavet Guy
• O'Brien Carol
• Pandita Ajay

Classifications

• C12Q1/6886 Primary

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

• A61K47/6809

  Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin · CPC title

• G01N33/15

  Medicinal preparations {; Physical properties thereof, e.g. dissolubility} · CPC title

• A61P15/14

  for lactation disorders, e.g. galactorrhoea · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title