Methods for predicting anti-cancer response

Patent metadata

Field	Value
Publication number	US-10190160-B2
Application number	US-201414466208-A
Country	US
Kind code	B2
Filing date	Aug 22, 2014
Priority date	Feb 23, 2012
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

Abstract

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

First claim

What is claimed is:

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.

Assignees

• Childrens Medical Center
• The Technical Univ Of Denmark
• Dana Farber Cancer Inst Inc
• Brigham & Womens Hospital Inc

Inventors

• Szallasi Zoltan
• Birkbak Nicolai Juul
• Eklund Aron
• Silver Daniel
• Wang Zhigang
• Richardson Andrea

Classifications

• C12Q2600/106

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

• C12Q2600/154

  Methylation markers · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6874 Primary

  involving nucleic acid arrays, e.g. sequencing by hybridisation · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title