Compositions and Methods for Treating Neoplasia
AssigneeGenesys Research Institute
InventorsNava Almog, Amir Abdollahi
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Abstract
The invention features compositions comprising microRNAs that are differentially regulated in dormant versus fast growing neoplasias, and related methods of using the microRNAs for inducing or prolonging dormancy in a neoplastic cell or otherwise inhibiting the growth of a neoplastic cell.
Claims62
A method of inhibiting neoplastic cell growth, comprising contacting a neoplastic cell with a dormancy associated microRNA.
A method of inhibiting tumor progression, comprising contacting a tumor with an effective amount of a dormancy associated microRNA.
A method of prolonging dormancy in a tumor, comprising contacting the tumor with an effective amount of a dormancy associated microRNA.
A method of inhibiting angiogenesis in a tumor, comprising administering to the subject an effective amount of a dormancy associated microRNA.
A method of ameliorating a neoplasia in a subject, comprising administering to the subject an effective amount of a dormancy associated microRNA.
A kit for the treatment of a neoplasia, the kit comprising an effective amount of a dormancy associated microRNA and directions for using the kit for the treatment of a neoplasia.
A pharmaceutical composition for the treatment of a neoplasia comprising an effective amount of a dormancy associated microRNA and a pharmaceutically acceptable excipient.
A method of characterizing the aggressiveness of a neoplasia, comprising determining the level of expression of one or more dormancy associated microRNAs in a subject sample, wherein a decreased level of expression relative to a reference indicates that the neoplasia is aggressive whereas an increased level of expression relative to a reference indicates that the neoplasia is dormant.
A method of characterizing the aggressiveness of a neoplasia, comprising determining the level of expression of one or more aggressiveness associated microRNAs in a subject sample, wherein an increased level of expression relative to a reference indicates that the neoplasia is aggressive, whereas a decreased level of expression relative to a reference indicates that the neoplasia is dormant.
A method of monitoring a subject diagnosed as having a neoplasia, the method comprising determining the level of expression of one or more dormancy associated microRNAs in a subject sample, wherein an alteration in the level of expression relative to the level of expression in a reference indicates the severity of neoplasia in a subject.
A method of monitoring a subject being treated for a neoplasia, the method comprising determining the level of expression of one or more aggressiveness associated microRNAs in a subject sample, wherein an alteration in the level of expression relative to the level of expression in a reference indicates the efficacy of the treatment in the subject.
A method of selecting a treatment regimen for a subject diagnosed as having a neoplasia, the method comprising determining the level of expression of one or more dormancy-associated or aggressive-associated microRNAs in a subject sample relative to a reference, wherein the level of expression of the microRNA indicates an appropriate treatment regimen for the subject.
A diagnostic kit for the diagnosis of a neoplasia in a subject comprising a nucleic acid probe capable of detecting a dormancy-associated microRNA and written instructions for use of the kit for detection of a neoplasia.
A method of altering the expression of a dormancy-associated microRNA in a cell, the method comprising contacting the cell with an effective amount of an agent capable of altering the expression of the dormancy-associated microRNA.
A method of identifying a compound that inhibits a neoplasia, the method comprising contacting a cell that expresses a dormancy-associated microRNA with a candidate agent, and comparing the level of expression of the microRNA in the cell with the level present in a control cell not contacted by the agent, wherein an increase in expression of the dormancy-associated microRNA identifies the agent as inhibiting a neoplasia.
A method of identifying an agent that inhibits a neoplasia, the method comprising contacting a cell that expresses an aggressiveness-associated microRNA with a candidate compound, and comparing the level of expression of the microRNA in the cell with the level present in a control cell not contacted by the agent, wherein reduced expression of the aggressiveness-associated microRNA identifies the agent as inhibiting a neoplasia.
A method of identifying a candidate agent that inhibits a neoplasia, the method comprising:
- a) contacting a cell containing a reporter molecule under control of a dormancy-associated microRNA promoter with a candidate compound;
- b) detecting the level of the reporter molecule expressed in the cell contacted with the candidate agent;
- and
- c) comparing the level of the reporter molecule expressed in the cell contacted with the candidate compound with the level of the reporter molecule expressed in a control cell not contacted with the candidate compound,
- wherein an alteration in the level of the reporter molecule expression identifies the candidate compound as a agent that inhibits neoplasia.
A method of inhibiting neoplastic cell growth, comprising contacting a neoplastic cell with an agent that inhibits the expression or activity of a protein or nucleic acid molecule that is down-regulated in response to Dmir overexpression in a neoplastic cell.
Dependencies are inferred from the claim text.