Methods for predicting anti-cancer response

Patent metadata

Field	Value
Publication number	US-11299782-B2
Application number	US-201816235247-A
Country	US
Kind code	B2
Filing date	Dec 28, 2018
Priority date	Feb 23, 2012
Publication date	Apr 12, 2022
Grant date	Apr 12, 2022

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, the method comprising:
(1) directing a clinical laboratory to
(a) detect a plurality of chromosomal aberrations in chromosomal segments comprising a plurality of loci in a sample from a human patient, 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 segments is at least 12 Mb in length, extends to and involves the telomere but does not cross the centromere,
(b) calculate a telomeric imbalance score (NtAI) by summing the number of chromosomal aberrations detected in step (a), and
(c) communicate an NtAI to the clinician, and
(2) administering 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 to the patient in whose sample an NtAI of at least 8 is calculated.

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 the 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. A method of administering an anti-cancer treatment to a human patient, the method comprising:
(1) receiving a telomeric imbalance score (NtAI) of at least 8 from a clinical laboratory, wherein the NtAI is determined by the steps of:
(a) detecting a plurality of chromosomal aberrations in chromosomal segments comprising a plurality of loci in a sample from a human patient, 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 segments is at least 12 Mb in length, extends to and involves the telomere but does not cross the centromere, and
(b) calculating the NtAI score by summing the number of chromosomal aberrations detected in step (a), and

(2) 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.

6. The method of claim 5 , wherein said detecting a plurality of chromosomal aberrations is in at least two, five, ten or 21 pairs of human chromosomes.

7. The method of claim 5 , wherein the 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.

8. The method of claim 5 , 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.

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

• C12Q1/6886 Primary

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

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/154

  Methylation markers · CPC title

• C12Q2600/158

  Expression markers · 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