Methods for predicting anti-cancer response
AssigneesChildren's Medical Center Corporation, Technical University of Denmark, Dana-Farber Cancer Institute, Inc., The Brigham and Women's Hospital, Inc.
InventorsZoltan SZALLASI, Nicolai Juul BIRKBAK, Aron EKLUND, Daniel SILVER, Zhigang WANG, Andrea RICHARDSON
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Abstract
The present invention is based, in part, on the identification of novel methods for defining predictive biomarkers of response to anti-cancer drugs.
Claims76
An assay for selecting therapy for a subject having cancer, the assay comprising
- subjecting a biological sample comprising a cancer cell or nucleic acid from a cancer cell taken from the subject to telomeric allelic imbalance (tAI) analysis;
- detecting the number of telomeric allelic imbalance (NtAI) in the cancer cell or nucleic acid from the cancer cell, and
- selecting a platinum-comprising therapy for the subject when the NtAI is detected to be above a reference value based on the recognition that platinum-comprising therapy is effective in patients who have NtAI above the reference value;
- and selecting a non-platinum-comprising cancer therapy for the subject when the NtAI is detected to be below a reference value based on the recognition that platinum-comprising cancer therapy is not effective in patients who have the NtAI below a reference value.
A method for selecting platinum-comprising therapy for a subject having cancer comprising
- subjecting a biological sample taken from the subject to allelic imbalance (AI) analysis;
- detecting the number of AI;
- and
- selecting platinum-comprising cancer therapy for the subject when the number of AIs is above a reference value based on the recognition that platinum-comprising cancer therapy is effective in patients who have the number of AIs is above a reference value.
A method comprising:
- detecting, in a cancer cell or genomic DNA derived therefrom, allelic imbalance in a representative number of pairs of human chromosomes of the cancer cell;
- and
- determining the number of allelic imbalance.
A method comprising:
- a) detecting, in a cancer cell or genomic DNA derived therefrom, LOH regions in a representative number of pairs of human chromosomes of the cancer cell;
- and
- b) determining the number and size of said LOH regions.
A method of determining prognosis in a patient comprising:
- a) determining whether the patient comprises cancer cells having an LOH signature, wherein the presence of more than a reference number of LOH regions in at least one pair of human chromosomes of a cancer cell of the cancer patient that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region indicates that the cancer cells have the LOH signature, wherein the at least one pair of human chromosomes is not a human X/Y sex chromosome pair, wherein the first length is about 1.5 or more megabases, an
- b) (1) determining, based at least in part on the presence of the LOH signature, that the patient has a relatively good prognosis, or b)(2) determining, based at least in part on the absence of the LOH signature, that the patient has a relatively poor prognosis
A composition comprising a therapeutic agent selected from the group consisting of DNA damaging agent, anthracycline, topoisomerase I inhibitor, and PARP inhibitor for use in treating a cancer selected from the group consisting of breast cancer, ovarian cancer, liver cancer, esophageal cancer, lung cancer, head and neck cancer, prostate cancer, colon cancer, rectal cancer, colorectal cancer, and pancreatic cancer in a patient with more than a reference number of LOH regions in at least one pair of human chromosomes of a cancer cell of the patient that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region, wherein the at least one pair of human chromosomes is not a human X/Y sex chromosome pair, wherein the first length is about 1.5 or more megabases.
A method of treating cancer in a patient, comprising:
- a) determining in a sample from said patient the number of LOH regions in at least one pair of human chromosomes of a cancer cell of the cancer patient that are longer than a first length but shorter than the length of the whole chromosome containing the LOH region indicates that the cancer cells have the LOH signature, wherein the at least one pair of human chromosomes is not a human X/Y sex chromosome pair, wherein the first length is about 1.5 or more megabases;
- b) providing a test value derived from the number of said LOH regions;
- c) comparing said test value to one or more reference values derived from the number of said LOH regions in a reference population (e.g., mean, median, terciles, quartiles, quintiles, etc.);
- and
- d) administering to said patient an anti-cancer drug, or recommending or prescribing or initiating a treatment regimen comprising chemotherapy and/or a synthetic lethality agent based at least in part on said comparing step revealing that the test value is greater (e.g., at least 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-fold greater;
- at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 standard deviations greater) than at least one said reference value;
- or
- e) recommending or prescribing or initiating a treatment regimen not comprising chemotherapy and/or a synthetic lethality agent based at least in part on said comparing step revealing that the test value is not greater (e.g., not more than 2-, 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-fold greater;
- not more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 standard deviations greater) than at least one said reference value.
A composition comprising a therapeutic agent selected from the group consisting of platinum comprising cancer therapy and anthracycline for use in treating a cancer selected from the group consisting of breast cancer, ovarian cancer, liver cancer, esophageal cancer, lung cancer, head and neck cancer, prostate cancer, colon cancer, rectal cancer, colorectal cancer, and pancreatic cancer in a patient with increased allelic imbalance.
A method for predicting the outcome of anti-cancer treatment of a subject with a cell hyperproliferative disorder, comprising determining a global chromosomal aberration score (GCAS), comprising obtaining a biological sample from the subject and determining whether a plurality of chromosomal regions displaying a chromosomal aberration exists within a plurality of chromosomal loci, wherein said chromosomal aberrations are selected from the group consisting of allelic imbalance (NAI), loss of heterozygosity (NLOH), copy number aberrations (NCNA), copy number gain (NCNG), copy number decrease (NCND) and combinations thereof, relative to a control, and wherein the presence of a plurality of chromosomal regions displaying said chromosomal aberrations predicts the outcome of anti-cancer treatment of the subject.
Dependencies are inferred from the claim text.