Use of opioid antagonists

Abstract

Embodiments of the invention provide methods of attenuating, e.g., inhibiting or reducing, cellular proliferation and migration, particularly endothelial cell proliferation and migration, including that associated with angiogenesis, as well as attenuating cancerous tumor growth and metastasis, using opioid antagonists, including, but not limited to, those that are peripherally restricted antagonists.

1 . A method of assessing responsiveness of cancer to treatment with a peripheral mu-opioid antagonist, comprising detecting the level of expression of the mu-opioid receptor (MOR) in a sample taken from a subject, and comparing the level of expression of the MOR in the sample with a standard value, wherein an increased level of expression is indicative of treatment responsiveness to the peripheral mu-opioid antagonist. 
     
     
         2 . The method of  claim 1 , wherein the sample is obtained from lung cancer tissue. 
     
     
         3 . The method of  claim 1 , wherein the increased level of expression is indicative of the therapeutic efficacy of the antagonist. 
     
     
         4 . The method of  claim 1 , wherein the peripheral mu-opioid antagonist is a quaternary or non-quaternary derivative of noroxymorphone. 
     
     
         5 . A method of predicting a clinical response to treatment with a peripheral opioid antagonist of a subject in need thereof, comprising detecting the expression level of MOR in a sample from the subject, and comparing the expression level of MOR in the sample from the subject with the expression level from a subject not in need of treatment, wherein increased expression of MOR is indicative of responsiveness to the opioid antagonist, and is predictive of a clinical response to treatment of with an opioid antagonist. 
     
     
         6 . The method of  claim 5 , wherein the peripheral mu-opioid antagonist is a quaternary or non-quaternary derivative of noroxymorphone. 
     
     
         7 . A method of assessing lung cancer prognosis, comprising detecting the MOR expression level in a specimen collected from a subject whose lung cancer prognosis is to be assessed; and comparing the level to a standard level, an elevated level indicative that the subject is suffering from lung cancer or is at risk of recurrence of lung cancer and that the lung cancer is responsive to MOR antagonist treatment; and treating the subject with a mu-opioid antagonist. 
     
     
         8 . The method of  claim 7 , wherein the peripheral mu-opioid antagonist is a quaternary or non-quaternary derivative of noroxymorphone. 
     
     
         9 . A method of attenuating tumor growth of a cancer, metastasis of a cancer, or both, in which the cancer comprises cells that overexpress mu-opioid receptors, comprising administering to a subject in need thereof an effective amount of a peripheral mu-opioid antagonist to attenuate the growth and/or metastasis. 
     
     
         10 . A method of achieving an effect in a subject, comprising administering to the subject an effective amount of a peripheral mu-opioid antagonist, wherein the effect is inhibiting cellular hyperproliferation, treating cancer, or inhibiting tumor growth.