Methods for predicting anti-cancer response

• US 10,190,160 B2
• Filed: 08/22/2014
• Issued: 01/29/2019
• Est. Priority Date: 02/23/2012
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, Dana-Farber Cancer Institute, Technical University of Denmark
• Original Assignee: Brigham and Women's Hospital Incorporated, Children's Medical Center Corporation, Dana-Farber Cancer Institute, Technical University of Denmark
• Inventors: Szallasi, Zoltan, Birkbak, Nicolai Juul, Eklund, Aron, Silver, Daniel, Wang, Zhigang, Richardson, Andrea
• Primary Examiner(s): Kapushoc, Stephen T
• Application Number:
  US14/466,208
• Publication Number:
  US 20150038340A1
• Time in Patent Office: 1,621 Days
• CPC Class Codes: C12Q 1/6874 involving nucleic acid arrays, e.g. sequencing by hybridisation
• 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 2600/154 Methylation markers
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

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 of administering an anti-cancer treatment to a human patient, comprising:

(a) detecting in a sample from a human patient, a plurality of chromosomal aberrations in chromosomal segments comprising a plurality of loci,

wherein chromosomal aberrations are detected in at least one pair of human chromosomes of a cancer cell of the patient,

wherein each of the chromosomal aberrations is at least 12 Mb in length, extends to and involves the telomere but does not cross the centromere, and

(b) calculating a telomeric imbalance score (NtAI) by summing the number of chromosomal aberrations detected in step (a);

(c) detecting an NtAI of at least 8; and

(d) administering to said patient an anti-cancer therapy selected from the group consisting of;

platinum-comprising therapy, DNA damaging agent-comprising therapy, anthracycline-comprising therapy, topoisomerase I inhibitor-comprising therapy and PARP inhibitor-comprising therapy.

2. The method of claim 1, wherein said detecting a plurality of chromosomal aberrations is in at least two, five, ten or 21 pairs of human chromosomes.

3. The method of claim 1, wherein said DNA damaging agent is cisplatin, carboplatin, oxalaplatin, or picoplatin, said anthracycline is epirubincin or doxorubicin, said topoisomerase I inhibitor is campothecin, topotecan, or irinotecan, and/or said PARP inhibitor is iniparib, olaparib or velapirib.

4. The method of claim 1, wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, melanoma, 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, and squamous cell carcinomas of the head, neck, cervix, colon cancer, or vagina.

5. The method of claim 1, wherein the number of chromosomal segments comprising a plurality of chromosomal aberrations is determined using major copy proportion (MCP).

6. The method of claim 5, wherein the number of chromosomal segments comprising a plurality of chromosomal aberrations for a given genomic region is counted when MCP is greater than 0.70.

7. The method of claim 1, wherein the NtAI score is at least 20.