LINE-1 Hypomethylation as a Biomarker for Early-Onset Colorectal Cancer
AssigneeBaylor Research Institute
InventorsAjay Goel, C. Richard Boland, Francesc Balaguer
Life of this patent
Estimating the term…
Abstract
A method for detecting an early-onset of colorectal cancer in a human subject is disclosed herein. The method comprises the steps of: (i) identifying the human subject suspected of suffering from a colorectal cancer, (ii) obtaining one or more biological samples from the human subject; (iii) determining a LINE-1 methylation level for the one or more biological samples; and (iv) comparing the LINE-1 methylation level to a LINE-1 methylation control level, wherein a higher degree of the LINE-1 methylation level is indicative of an early-onset colorectal cancer.
Claims23
A method for predicting, detecting, diagnosing or monitoring pre-cancer or cancer in a human subject comprising the steps of:
- obtaining one or more biological samples from the human subject;
- determining a LINE-1 methylation level for the one or more biological samples;
- and
- comparing the LINE-1 methylation level to a LINE-1 methylation control level, wherein a lower degree of the LINE-1 methylation level is indicative of an early-onset colorectal cancer.
A biomarker for predicting, detecting, diagnosing or monitoring an early-onset of colorectal cancer in a human subject comprising:
- a biomarker to determine a methylation level of LINE-1, wherein a lower methylation level of LINE-1 is indicative of an early-onset colorectal cancer in the human subject.
A kit for determining an early-onset of colorectal cancer in a human subject comprising:
- a biomarker detecting reagent for measuring a LINE-1 methylation level in a sample;
- and
- instructions for the use of the biomarker detecting reagent in diagnosing the presence of early-onset of colorectal cancer, wherein the instructions comprise providing step-by-step directions to compare the LINE-1 methylation level in the sample with a LINE-1 methylation control level.
A method for selecting a cancer therapy for a patient diagnosed with early-onset of colorectal cancer, the method comprising the steps of:
- determining a methylation level of LINE-1 in a biological samples of the subject, wherein the methylation level of LINE-1 is indicative of early-onset of colorectal cancer;
- and
- selecting the cancer therapy based on the determination of the presence of early-onset of colorectal cancer in the subject.
A method of performing a clinical trial to evaluate a candidate drug believed to be useful in treating early-onset of colorectal cancer, the method comprising:
- a) determining the presence of an early-onset of colorectal cancer by a method comprising the steps of:
- determining an overall LINE-1 methylation level in one or more cells obtained from a biological sample of the subject, wherein a lower overall LINE-1 methylation level compared to a reference control is indicative of an early-onset of colorectal cancer;
- b) administering a candidate drug to a first subset of the patients, and
- a placebo to a second subset of the patients;
- a comparable drug to a second subset of the patients;
- or
- a drug combination of the candidate drug and another active agent to a second subset of patients;
- c) repeating step a) after the administration of the candidate drug or the placebo, the comparable drug or the drug combination;
- and
- d) monitoring a change in the overall LINE-1 methylation level as compared to any reduction occurring in the second subset of patients, wherein a statistically significant reduction indicates that the candidate drug is useful in treating said disease state.
A method for detecting a pre-cancer or an early-onset of colorectal cancer in a human subject comprising the steps of:
- identifying the human subject suspected of suffering from a colorectal cancer;
- obtaining one or more biological samples from the human subject;
- determining a LINE-1 methylation level for the one or more biological samples;
- and
- comparing the LINE-1 methylation level to a LINE-1 methylation control level, wherein a lower degree of the LINE-1 methylation level is indicative of an early-onset colorectal cancer.
A method for detecting pre-cancer or cancer in a human subject comprising the steps of:
- obtaining one or more biological samples from the human subject;
- processing the one or more biological samples to determine a LINE-1 methylation level for the one or more biological samples;
- and
- comparing the LINE-1 methylation level from the one or more biological samples to a LINE-1 methylation level from a normal colorectal tissue, wherein a lower degree of the LINE-1 methylation level is indicative of an early-onset colorectal cancer.
A method of using a pharmacodynamic (PD) biomarker for determining a pharmacological response to a treatment of an early-onset of colorectal cancer, the method comprising:
- determining an overall LINE-1 methylation level in one or more cells obtained from a first biological sample of a subject, wherein a lower overall LINE-1 methylation level compared to a normal sample from the subject that is not suspected of having cancer, is indicative of an early-onset of colorectal cancer;
- administering a drug to the subject at a first time,
- repeating the step of determining an overall LINE-1 methylation level in one or more cells obtained from a second biological sample from the subject at a second time;
- and
- comparing the overall LINE-1 methylation at the first and the second time, wherein a statistically significant reduction in LINE-1 methylation indicates that the drug is useful in treating the early-onset of colorectal cancer.
Dependencies are inferred from the claim text.