Compostions, kits, and methods for identification, assessment, prevention, and therapy of cancer
AssigneesDana-Farber Cancer Institute, Inc., Board of Trustees of the University of Arkansas
InventorsRonald DePinho, Kenneth Anderson, Ruben Carresco, Giovanni Tonon, Cameron Brennan, John Shaughnessy, Lynda Chin
Life of this patent
Estimating the term…
Abstract
The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.
Claims167
A method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, the method comprising comparing the copy number of a minimal common region (MCR) in a subject sample to the normal copy number of the MCR, wherein said MCR is selected from the group consisting of the MCRs listed in Tables 1 or 2, and wherein an altered copy number of the MCR in the sample indicates that the subject is afflicted with cancer or at risk for developing cancer.
A method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, the method comprising comparing:
- a) the amount, structure, and/or activity of a marker in a subject sample, wherein the marker is a marker which resides in an MCR listed in Tables 1 or 2;
- and
- b) the normal amount, structure, and/or activity of the of the marker,
- wherein a significant difference between the amount, structure, and/or activity of the marker in the sample and the normal amount, structure, and/or activity is an indication that the subject is afflicted with cancer or at risk for developing cancer.
A method for monitoring the progression of cancer in a subject, the method comprising:
- a) detecting in a subject sample at a first point in time, the amount and/or activity of a marker, wherein the marker is a marker which resides in an MCR listed in Tables 1 or 2;
- b) repeating step a) at a subsequent point in time;
- and
- c) comparing the amount and/or activity detected in steps a) and b), and therefrom monitoring the progression of cancer in the subject.
A method of assessing the efficacy of a test compound for inhibiting cancer in a subject, the method comprising comparing:
- a) the amount and/or activity of a marker in a first sample obtained from the subject and maintained in the presence of the test compound, wherein the marker is a marker which resides in an MCR listed in Tables 1 or 2;
- and
- b) the amount and/or activity of the marker in a second sample obtained from the subject and maintained in the absence of the test compound,
- wherein a significantly higher amount and/or activity of a marker in the first sample residing in an MCR which is deleted in cancer, relative to the second sample, is an indication that the test compound is efficacious for inhibiting cancer, and wherein a significantly lower amount and/or activity of a marker in the first sample residing in an MCR which is amplified in cancer, relative to the second sample, is an indication that the test compound is efficacious for inhibiting cancer in the subject.
A method of assessing the efficacy of a therapy for inhibiting cancer in a subject, the method comprising comparing:
- a) the amount and/or activity of a marker in the first sample obtained from the subject prior to providing at least a portion of the therapy to the subject, wherein the marker is a marker which resides in an MCR listed in Tables 1 or 2, and
- b) the amount and/or activity of the marker in a second sample obtained from the subject following provision of the portion of the therapy,
- wherein a significantly higher amount and/or activity of the marker in the first sample residing in an MCR which is deleted in cancer, relative to the second sample, is an indication that the test compound is efficacious for inhibiting cancer and wherein a significantly lower amount and/or activity of the marker in the first sample residing in an MCR which is amplified in cancer, relative to the second sample, is an indication that the therapy is efficacious for inhibiting cancer in the subject.
A method of selecting a composition capable of modulating cancer, the method comprising:
- a) obtaining a sample comprising cancer cells;
- b) contacting said cells with a test compound;
- and
- c) determining the ability of the test compound to modulate the amount and/or activity of a marker, wherein the marker is a marker which resides in an MCR listed in Tables 1 or 2,
- thereby identifying a modulator of cancer.
A method of selecting a composition capable of modulating cancer, the method comprising:
- a) contacting a marker which resides in an MCR listed in Tables 1 or 2 with a test compound;
- and
- b) determining the ability of the test compound to modulate the amount and/or activity of a marker which resides in an MCR listed in Tables 1 or 2,
- thereby identifying a composition capable of modulating cancer.
A kit for assessing the ability of a compound to inhibit cancer, the kit comprising a reagent for assessing the amount, structure, and/or activity of a marker which resides in an MCR listed in Tables 1 or 2.
A kit for assessing whether a subject is afflicted with cancer, the kit comprising a reagent for assessing the copy number of an MCR selected from the group consisting of the MCRs listed in Tables 1 or 2.
A kit for assessing whether a subject is afflicted with cancer, the kit comprising a reagent for assessing the amount, structure, and/or activity of a marker which resides in an MCR listed in Tables 1 or 2.
A kit for assessing the presence of human cancer cells, the kit comprising an antibody or fragment thereof, wherein the antibody or fragment thereof specifically binds with a protein corresponding to a marker which resides in an MCR listed in Tables 1 or 2.
A kit for assessing the presence of cancer cells, the kit comprising a nucleic acid probe wherein the probe specifically binds with a transcribed polynucleotide corresponding to a marker which resides in an MCR listed in Tables 1 or 2.
A method of treating a subject afflicted with cancer comprising administering to the subject a modulator of amount and/or activity of a gene or protein corresponding to a marker which resides in an MCR listed in Tables 1 or 2, thereby treating a subject afflicted with cancer.
A method of treating a subject afflicted with cancer comprising administering to the subject a compound which inhibits the amount and/or activity of a gene or protein corresponding to a marker which resides in an MCR listed in Table 1, which is amplified in cancer, thereby treating a subject afflicted with cancer.
A method of treating a subject afflicted with cancer comprising administering to the subject a compound which increases expression or activity of a gene or protein corresponding to a marker which resides in an MCR listed in Table 2 which is deleted in cancer, thereby treating a subject afflicted with cancer.
A method of treating a subject afflicted with cancer comprising administering to the subject a protein corresponding to a marker which resides in an MCR listed in Table 2, which is deleted in cancer, thereby treating a subject afflicted with cancer.
An isolated protein, or fragment thereof, corresponding to a marker selected from the markers listed in Tables 4 or 5.
An isolated nucleic acid molecule, or fragment thereof, corresponding to a marker selected from the markers listed in Tables 4 or 5.
An isolated antibody, or fragment thereof, which specifically binds to a protein corresponding to a marker selected from the markers listed in Tables 4 or 5.
An isolated nucleic acid molecule, or fragment thereof, contained within an MCR selected from the MCRs listed in Tables 1 or 2, wherein said nucleic acid molecule has an altered amount, structure, and/or activity in cancer.
A method for identifying a marker associated with cancer, said method comprising:
- a) performing profiling of the genome of cancer cells;
- b) performing segmentation analysis of profiles identified in step a);
- c) identifying loci;
- d) prioritizing said identified loci;
- and
- e) interrogating genes in the identified loci,
- to thereby identify a marker associated with cancer.
A method for identifying a locus associated with cancer, said method comprising the steps of:
- a) performing profiling of the genome of cancer cells;
- b) performing segmentation analysis of profiles identified in step a);
- c) identifying loci;
- and
- d) prioritizing said identified loci,
- to thereby identify a locus associated with cancer.
A method of assessing whether a subject is afflicted with cancer or at risk for developing cancer, the method comprising comparing:
- a) the amount, structure, and/or activity of a marker in a subject sample, wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof;
- and
- b) the normal amount, structure, and/or activity of the of the marker,
- wherein a significant difference between the amount, structure, and/or activity of the marker in the sample and the normal amount, structure, and/or activity is an indication that the subject is afflicted with cancer or at risk for developing cancer.
A method for monitoring the progression of cancer in a subject, the method comprising:
- a) detecting in a subject sample at a first point in time, the amount and/or activity of a marker, wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof;
- and
- b) repeating step a) at a subsequent point in time;
- and
- c) comparing the amount and/or activity detected in steps a) and b), and therefrom monitoring the progression of cancer in the subject.
A method of assessing the efficacy of a test compound for inhibiting cancer in a subject, the method comprising comparing:
- a) the amount and/or activity of a marker in a first sample obtained from the subject and maintained in the presence of the test compound, wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof;
- and
- b) the amount and/or activity of the marker in a second sample obtained from the subject and maintained in the absence of the test compound,
- wherein a significantly lower amount and/or activity of a marker in the first sample relative to the second sample, is an indication that the test compound is efficacious for inhibiting cancer.
A method of assessing the efficacy of a therapy for inhibiting cancer in a subject, the method comprising comparing:
- a) the amount and/or activity of a marker in the first sample obtained from the subject prior to providing at least a portion of the therapy to the subject, wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof;
- and
- b) the amount and/or activity of the marker in a second sample obtained from the subject following provision of the portion of the therapy,
- wherein a significantly lower amount and/or activity of the marker in the first sample relative to the second sample, is an indication that the test compound is efficacious for inhibiting cancer.
A method of selecting a composition capable of modulating cancer, the method comprising:
- a) obtaining a sample comprising cancer cells;
- b) contacting said cells with a test compound;
- and
- c) determining the ability of the test compound to modulate the amount and/or activity of a marker, wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof;
- and thereby identifying a modulator of cancer.
A method of selecting a composition capable of modulating cancer, the method comprising:
- a) contacting a marker selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof with a test compound;
- and
- b) determining the ability of the test compound to modulate the amount and/or activity of a marker selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof;
- and thereby identifying a composition capable of modulating cancer.
A kit for assessing the ability of a compound to inhibit cancer, the kit comprising a reagent for assessing the amount, structure, and/or activity of a marker is selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof.
A kit for assessing whether a subject is afflicted with cancer, the kit comprising a reagent for assessing the amount, structure, and/or activity of a marker wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36, GPR86, and combinations thereof.
A kit for assessing the presence of human cancer cells, the kit comprising an antibody or fragment thereof, wherein the antibody or fragment thereof specifically binds with a protein corresponding to a marker selected from the group consisting of PRKCi, SEMA4A, DHH36 and GPR86.
A kit for assessing the presence of cancer cells, the kit comprising a nucleic acid probe wherein the probe specifically binds with a transcribed polynucleotide corresponding to a marker selected from the group consisting of PRKCi, SEMA4A, DHH36 and GPR86.
A method of treating a subject afflicted with cancer comprising administering to the subject a modulator of amount and/or activity of a gene or protein corresponding to a marker wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36 and GPR86, and thereby treating a subject afflicted with cancer.
A method of treating a subject afflicted with cancer comprising administering to the subject a compound which inhibits the amount and/or activity of a gene or protein corresponding to a marker wherein the marker is selected from the group consisting of PRKCi, SEMA4A, DHH36 and GPR86 and thereby treating a subject afflicted with cancer.
Dependencies are inferred from the claim text.