Cancer Markers
AssigneeIFOM Fondazione Instituto FIRC di Oncologia Molecolare
InventorsPier Paolo Di Fiore, Salvatore Pece, Ian Marc Bonapace, Francesco Nicassio, Fabrizio Bianchi, Manuela Vecchi, Stefano Confalonieri
Life of this patent
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Abstract
The invention related to methods of diagnosis and prognosis of cancer, the methods comprising determining the level of one or more gene products. In addition, the invention relates to modulators of the gene products for use in treatment of cancer. The genes include EIA-induced genes and Numb.
Claims68
A method of providing an indicator for assessment of cancer in a patient, the method comprising:
- providing an assay sample of tissue obtained from said patient;
- and
- determining the Numb status of said sample.
The method of any one of the preceding claims, wherein the cancer is breast cancer.
The method of any one of the preceding claims wherein the method further comprises determining the status in the assay sample of one or more further proteins which are associated with prognosis or diagnosis of the cancer.
The method of any one of the preceding claims, which further comprises determining the level of Notch activity in said sample.
The method of any one of the preceding claims, wherein the method further comprises determining the expression level of one or more genes which is transcriptionally regulated by Notch.
A kit for use in the assessment of cancer, the kit comprising a specific binding partner for a Numb gene expression product, and a specific binding partner for at least one other gene expression product associated with prognosis or diagnosis in the cancer.
A kit for the assessment of cancer comprising a specific binding partner of a Numb gene expression product, wherein said binding partner is immobilised on a solid support.
Use a specific binding partner of a Numb expression product for the manufacture of a kit for the assessment of cancer in a patient.
A method of determining susceptibility of a tumour in a patient to treatment with an inhibitor of Notch signalling, the method comprising:
- providing an assay sample of tumour tissue obtained from said patient;
- and
- determining the Numb status of said sample.
Use of an inhibitor of Notch signalling in the manufacture of a medicament for the treatment of cancer in a patient, wherein said patient has reduced Numb activity in a tumour relative to a control sample.
A method of screening for a candidate agent for the treatment of cancer in a patient, comprising:
- providing a test system comprising a Numb polypeptide and an enzyme capable of targeting Numb for degradation;
- contacting said test system with a test agent;
- and assessing the ability of the test agent to inhibit the targeting of Numb for degradation.
A method of selecting a specific binding partner of a gene expression product for use in providing an indicator for the assessment of cancer, comprising:
- identifying a gene whose expression is modulated by contacting a terminally differentiated mammalian cell in culture with an agent which causes re-entry of the cell into the cell cycle;
- and
- selecting a specific binding partner for an expression product of said gene.
A method of providing an indicator for assessment of cancer in a patient, the method comprising:
- providing an assay sample of tissue obtained from said patient;
- determining the level in the sample of an expression product of at least one gene selected from DDX21, SF3B1, ch-TOG, SKIN, TRPC4AP and SMU-1, or other genes listed in FIG. 11.
A method of providing an indicator for assessment of breast cancer in a patient comprising:
- providing an assay sample of tissue obtained from said patient;
- and
- determining the level in said sample of an expression product of at least one gene from table 2.
A method of providing an indicator for assessment of NSCLC in a patient comprising:
- providing an assay sample of tissue obtained from said patient;
- and
- determining the level in said sample of an expression product of at least one gene from table 3 or table 4.
A kit for use in the assessment of cancer, wherein the kit comprises a specific binding partner for the expression product of:
- at least one gene selected from DDX21, SF3B1, ch-TOG, SKIN, TRPC4AP and SMU-1, or other gene listed in FIG. 11;
- or
- at least one of ch-TOG, SKIN, and TRPC4AP;
- at least one of SKIN, SMU-1 and ch-TOG;
- or
- at least one gene from table 2;
- or
- at least one gene from table 3 or table 4,
- wherein said specific binding partner is immobilised on a solid surface.
Use of a specific binding partner of:
- a gene selected from DDX21, SF3B1, ch-TOG, SKIN, TRPC4AP and SMU-1, or other gene listed in FIG. 11;
- or
- a gene selected from table 2;
- or
- a gene selected from table 3 or table 4, in the manufacture of a kit for use in providing an indicator for the assessment of cancer.
A method of screening for a candidate agent for the treatment of cancer in a patient, comprising:
- a) providing a protein selected from DDX21, SF3B1, ch-TOG, SKIN, TRPC4AP and SMU-1 or other gene listed in FIG. 11, or a protein of table 2, table 3 or table 4;
- b) bringing the protein into contact with a test agent;
- c) determining whether said test agent is capable of binding and/or modulating the activity of the protein.
A method of screening for a candidate agent for the treatment of cancer in a patient, comprising:
- identifying a gene whose expression is modulated in a terminally differentiated mammalian cell in culture by contacting the cell with an agent which causes its re-entry into the cell cycle;
- providing a protein expressed by the gene;
- bringing the protein into contact with a test agent;
- and
- determining whether said test agent is capable of binding and/or modulating the activity of the protein.
A method of screening for a candidate agent for the treatment of cancer in a patient, wherein said method comprises
- a) providing a transformed cell in culture;
- b) bringing said cell into contact with a test agent and
- c) determining whether said test agent is capable of modulating the level of a transcript selected from DDX21, SF3B1, CH-TOG, SKIN, TRPC4AP and SMU-1 or other transcripts listed in FIG. 11 or a transcript of table 2, table 3 or table 4.
A method of screening for a candidate agent for the treatment of cancer in a patient, comprising:
- identifying a gene whose expression is modulated in a terminally differentiated mammalian cell in culture by contacting the cell with an agent which causes its re-entry into the cell cycle;
- providing a transformed cell in culture:
- bringing said cell into contact with a test agent;
- determining whether said test agent is capable of modulating the level of the transcript of said gene.
A method according to claim 60 wherein the expression of said gene is not strongly modulated by inactivation of a pocket protein, and is significantly modulated by an EIA pocket binding mutant. A screening method according to claim 66 or claim 67, rein the agent which causes re-entry into the cell cycle is
A screening method according to any one of claims 66 to wherein said test agent is an antisense oligonucleotide or RNAi. Use of an agent obtainable in a screening method of any of claims 59 to 69 for the manufacture of a medicament for treatment of cancer.
Dependencies are inferred from the claim text.