Methods for predicting anti-cancer response

• US 10,577,662 B2
• Filed: 10/20/2016
• Issued: 03/03/2020
• Est. Priority Date: 08/24/2010
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, Dana-Farber Cancer Institute, Technical University of Denmark
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Richardson, Andrea L., Wang, Zhigang C., Silver, Daniel P., Szallasi, Zoltan, Birkbak, Nicolai Juul, Eklund, Aron Charles
• Primary Examiner(s): Kapushoc, Stephen T
• Application Number:
  US15/298,728
• Publication Number:
  US 20170037478A1
• Time in Patent Office: 1,230 Days
• 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 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: C12Q 2600/172 Haplotypes

Abstract

The present invention is based, in part, on the identification of novel methods for defining predictive biomarkers of response to anti-cancer drugs.

Claims

1. A method for administering anti-cancer treatment comprising a PARP inhibitor to a human patient, the method comprising:

(1) assaying DNA in or derived from a hyperproliferative cell sample to

(a) detect copy number at a plurality of polymorphic chromosomal loci, wherein the plurality of polymorphic chromosomal loci comprises at least 1,000 polymorphic chromosomal loci and wherein there is at least one polymorphic chromosomal locus located on average every 500 kb within each chromosome; and

(b) detect, based on the copy number detected in (a), allelic imbalance regions having a minimum segment size of 12 Mb that extend to and involve the telomere and do not cross the centromere;

(2) calculating a test global chromosomal aberration score (GCAS) for the hyperproliferative cell sample determined by summing the total number of allelic imbalance regions detected in (1)(b);

(3) detecting a global chromosomal aberration score of at least 8; and

(4) administering anti-cancer treatment comprising a PARP inhibitor to the human patient.

2. The method of claim 1, wherein the PARP inhibitor is selected from the group consisting of olaparib, ABT-888, BSI-201, BGP-15, INO-1001, PJ34, 3-aminobenzamide, 4-amino-1,8-naphthalimide, 6(5H)-phenanthridinone, benzamide and NU1025.

3. The method of claim 1, wherein the PARP inhibitor is selected from the group consisting of olaparib and ABT-888.

4. The method of claim 1, wherein the hyperproliferative cell sample is from a patient having a cell hyperproliferative disorder selected from the group consisting of:

breast cancer, ovarian cancer, transitional cell bladder cancer, bronchogenic lung cancer, thyroid cancer, pancreatic cancer, prostate cancer, uterine cancer, testicular cancer, gastric cancer, soft tissue and osteogenic sarcomas, neuroblastoma, Wilms'"'"' tumor, malignant lymphoma (Hodgkin'"'"'s and non-Hodgkin'"'"'s), acute myeloblastic leukemia, acute lymphoblastic leukemia, Kaposi'"'"'s sarcoma, Ewing'"'"'s tumor, refractory multiple myeloma, colon cancer, melanoma, and squamous cell carcinomas of the head, neck, cervix, and vagina.

5. The method of claim 4, wherein the hyperproliferative cell sample is selected from the group consisting of cells, cell lines, histological slides, frozen core biopsies, paraffin embedded tissues, formalin fixed tissues, biopsies, whole blood, nipple aspirate, serum, plasma, buccal scrape, saliva, cerebrospinal fluid, urine, stool, and bone marrow.

6. The method of claim 4, wherein the hyperproliferative cell sample is enriched for the presence of hyperproliferative cells to at least 75% of the total population of cells.

7. The method of claim 6, wherein the enrichment is performed according to at least one technique selected from the group consisting of needle microdissection, laser microdissection, fluorescence activated cell sorting, and immunological cell sorting.

8. The method of claim 7, wherein an automated machine performs the at least one technique to thereby transform the hyperproliferative cell sample into a purified form enriched for the presence of hyperproliferative cells.

9. The method of claim 1, wherein the hyperproliferative cell sample is obtained before the subject has received adjuvant chemotherapy.

10. The method of claim 1, wherein the hyperproliferative cell sample is obtained after the subject has received adjuvant chemotherapy.

11. The method of claim 1, wherein allelic imbalance is detected in (2) using major copy proportion.

12. The method of claim 11, wherein an allelic imbalance region is detected in (2) when MCP is greater than 0.70.

13. The method of claim 1, wherein the plurality of polymorphic chromosomal loci comprises at least one polymorphic chromosomal locus located on average every 100 kb within each chromosome.

14. The method of claim 1, wherein the plurality of polymorphic chromosomal loci comprise at least one polymorphic chromosomal locus on each of the 23 human chromosome pairs.

15. The method of claim 1, wherein the plurality of polymorphic chromosomal loci comprise at least one polymorphic chromosomal locus on each arm of each of the 23 human chromosome pairs.

16. The method of claim 15, wherein the plurality of polymorphic chromosomal loci comprise at least one polymorphic chromosomal locus on at least one telomere of each of the 23 human chromosome pairs.

17. The method of claim 16, wherein the plurality of polymorphic chromosomal loci comprise at least one polymorphic chromosomal locus on each telomere of each of the 23 human chromosome pairs.

18. The method of claim 1, wherein the number of allelic imbalance regions detected comprises at least 5 chromosomal aberrations.

19. The method of claim 18, wherein the number of allelic imbalance regions detected comprises at least 13 chromosomal aberrations.

20. The method of claim 1, wherein the polymorphic chromosomal loci are selected from the group consisting of single nucleotide polymorphisms (SNPs), restriction fragment length polymorphisms (RFLPs), and simple tandem repeats (STRs).

21. The method of claim 1, wherein the polymorphic chromosomal loci are genotyped using at least one technique selected from the group consisting of molecular inversion probe (MIP), single nucleotide polymorphism (SNP) array, in situ hybridization, Southern blotting, transcriptional arrays, array comparative genomic hybridization (aCGH), and next-generation sequencing.

22. The method of claim 1, wherein said DNA is derived from said hyperproliferative cell sample by extracting nuclear DNA from the hyperproliferative cell sample by a technique comprising:

(i) contacting the hyperproliferative cell sample with proteinase K and/or RNase A,

(ii) performing a phenol/chloroform extraction on the mixture of step (i), and

(iii) performing an ethanol precipitation on the extracted DNA of step (ii).