Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors
AssigneeSignal Pharmaceuticals, LLC
InventorsRajesh Chopra, Yuhong Ning, Sabita Sankar, Shuichan Xu, Weiming Xu
Life of this patent
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Abstract
Provided herein are methods for treating and/or preventing a cancer or a tumor syndrome in a patient, comprising administering an effective amount of a TOR kinase inhibitor to a patient having cancer or a tumor syndrome, characterized by a LKB1 and/or AMPK gene or protein loss or mutation.
Claims25
A method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, comprising administering an effective amount of a TOR kinase inhibitor to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome characterized by a LKB1 gene or protein loss or mutation, relative to wild type.
A method for treating non-small cell lung carcinoma or cervical cancer, comprising screening a patient's carcinoma or cancer for the presence of LKB1 gene or protein loss or mutation, relative to wild type, and administering an effective amount of a TOR kinase inhibitor to the patient having non-small cell lung carcinoma or cervical cancer characterized by LKB1 gene or protein loss or mutation.
A method for predicting the likelihood of a patient having non-small cell lung carcinoma or cervical cancer being responsive to TOR kinase inhibitor therapy, comprising screening said patient's carcinoma or cancer for the presence of LKB1 gene or protein loss or mutation, relative to wild type, wherein the presence of LKB1 gene or protein loss or mutation predicts an increased likelihood that TOR kinase inhibitor therapy will treat said non-small cell lung carcinoma or cervical cancer.
A method for predicting therapeutic efficacy of treatment of a patient having non-small cell lung carcinoma or cervical cancer with a TOR kinase inhibitor, comprising screening said patient's carcinoma or cancer for the presence of LKB1 gene or protein loss or mutation, relative to wild type, wherein the presence of LKB1 gene or protein loss or mutation is predictive of therapeutic efficacy of treatment with a TOR kinase inhibitor.
A method for treating Peutz-Jeghers Syndrome, comprising screening a patient for the presence of LKB1 gene or protein loss or mutation, relative to wild type, and administering an effective amount of a TOR kinase inhibitor to the patient having Peutz-Jeghers Syndrome characterized by LKB1 gene or protein loss or mutation.
A method for predicting the likelihood of a patient having Peutz-Jeghers Syndrome being responsive to TOR kinase inhibitor therapy, comprising screening said patient for the presence of LKB1 gene or protein loss or mutation, relative to wild type, wherein the presence of LKB1 gene or protein loss or mutation predicts an increased likelihood that TOR kinase inhibitor therapy will treat said Peutz-Jeghers Syndrome.
A method for predicting therapeutic efficacy of treatment of a patient having Peutz-Jeghers Syndrome with a TOR kinase inhibitor, comprising screening said patient for the presence of LKB1 gene or protein loss or mutation, relative to wild type, wherein the presence of LKB1 gene or protein loss or mutation is predictive of therapeutic efficacy of treatment with a TOR kinase inhibitor.
A method for treating non-small cell lung carcinoma or cervical cancer or Peutz-Jeghers Syndrome, comprising administering an effective amount of a TOR kinase inhibitor and an effective amount of one or more agents that modulate AMP levels, glucose uptake, metabolism or a stress response to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome.
A pharmaceutical composition comprising a TOR kinase inhibitor and one or more agents that modulate AMP levels, glucose uptake, metabolism or a stress response, and a pharmaceutically acceptable carrier, excipient or diluent.
A kit comprising one or more containers filled with a TOR kinase inhibitor or a pharmaceutical composition thereof, reagents for detecting LKB1 gene or protein loss or mutation, AMPK gene or protein loss or mutation, or both, relative to wild type, in a patient's cancer or in a patient having a tumor syndrome and instructions for detecting LKB1 gene or protein loss or mutation, AMPK gene or protein loss or mutation, or both, in a patient's cancer or in a patient having a tumor syndrome.
A method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, comprising administering an effective amount of a TOR kinase inhibitor to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome characterized by a AMPK gene or protein loss or mutation, relative to wild type.
A method for treating non-small cell lung carcinoma or cervical cancer, comprising screening a patient's carcinoma or cancer for the presence of AMPK gene or protein loss or mutation, relative to wild type, and administering an effective amount of a TOR kinase inhibitor to the patient having non-small cell lung carcinoma or cervical cancer characterized by AMPK gene or protein loss or mutation.
A method for predicting the likelihood of a patient having non-small cell lung carcinoma or cervical cancer being responsive to TOR kinase inhibitor therapy, comprising screening said patient's carcinoma or cancer for the presence of AMPK gene or protein loss or mutation, relative to wild type, wherein the presence of AMPK gene or protein loss or mutation predicts an increased likelihood that TOR kinase inhibitor therapy will treat said non-small cell lung carcinoma or cervical cancer.
A method for predicting therapeutic efficacy of treatment of a patient having non-small cell lung carcinoma or cervical cancer with a TOR kinase inhibitor, comprising screening said patient's carcinoma or cancer for the presence of AMPK gene or protein loss or mutation, relative to wild type, wherein the presence of AMPK gene or protein loss or mutation is predictive of therapeutic efficacy of treatment with a TOR kinase inhibitor.
A method for treating Peutz-Jeghers Syndrome, comprising screening a patient for the presence of AMPK gene or protein loss or mutation, relative to wild type, and administering an effective amount of a TOR kinase inhibitor to the patient having Peutz-Jeghers Syndrome characterized by AMPK gene or protein loss or mutation.
A method for predicting the likelihood of a patient having Peutz-Jeghers Syndrome being responsive to TOR kinase inhibitor therapy, comprising screening said patient for the presence of AMPK gene or protein loss or mutation, relative to wild type, wherein the presence of AMPK gene or protein loss or mutation predicts an increased likelihood that TOR kinase inhibitor therapy will treat said Peutz-Jeghers Syndrome.
A method for predicting therapeutic efficacy of treatment of a patient having Peutz-Jeghers Syndrome with a TOR kinase inhibitor, comprising screening said patient for the presence of AMPK gene or protein loss or mutation, relative to wild type, wherein the presence of AMPK gene or protein loss or mutation is predictive of therapeutic efficacy of treatment with a TOR kinase inhibitor.
A method for treating non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome, comprising administering an effective amount of a TOR kinase inhibitor to a patient having non-small cell lung carcinoma, cervical cancer or Peutz-Jeghers Syndrome characterized by a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type.
A method for treating non-small cell lung carcinoma or cervical cancer, comprising screening a patient's carcinoma or cancer for the presence of a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type, and administering an effective amount of a TOR kinase inhibitor to the patient having non-small cell lung carcinoma or cervical cancer characterized by a reduced level of pAMPK protein, AMPK activity, or both.
A method for predicting the likelihood of a patient having non-small cell lung carcinoma or cervical cancer being responsive to TOR kinase inhibitor therapy, comprising screening said patient's carcinoma or cancer for the presence of a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type, wherein the presence of a reduced level of pAMPK protein, AMPK activity, or both, predicts an increased likelihood that TOR kinase inhibitor therapy will treat said non-small cell lung carcinoma or cervical cancer.
A method for predicting therapeutic efficacy of treatment of a patient having non-small cell lung carcinoma or cervical cancer with a TOR kinase inhibitor, comprising screening said patient's carcinoma or cancer for the presence of a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type, wherein the presence of a reduced level of pAMPK protein, AMPK activity, or both, is predictive of therapeutic efficacy of treatment with a TOR kinase inhibitor.
A method for treating Peutz-Jeghers Syndrome, comprising screening a patient for the presence of a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type, and administering an effective amount of a TOR kinase inhibitor to the patient having Peutz-Jeghers Syndrome characterized by a reduced level of pAMPK protein, AMPK activity, or both.
A method for predicting the likelihood of a patient having Peutz-Jeghers Syndrome being responsive to TOR kinase inhibitor therapy, comprising screening said patient for the presence of a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type, wherein the presence of a reduced level of pAMPK protein, AMPK activity, or both, predicts an increased likelihood that TOR kinase inhibitor therapy will treat said Peutz-Jeghers Syndrome.
A method for predicting therapeutic efficacy of treatment of a patient having Peutz-Jeghers Syndrome with a TOR kinase inhibitor, comprising screening said patient for the presence of a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type, wherein the presence of a reduced level of pAMPK protein, AMPK activity, or both, is predictive of therapeutic efficacy of treatment with a TOR kinase inhibitor.
A kit comprising one or more containers filled with a TOR kinase inhibitor or a pharmaceutical composition thereof, reagents for detecting a reduced level of pAMPK protein, AMPK activity, or both, relative to wild type, in a patient's cancer or in a patient having a tumor syndrome and instructions for detecting a reduced level of pAMPK protein and/or AMPK activity in a patient's cancer or in a patient having a tumor syndrome.
Dependencies are inferred from the claim text.