Methods and compositions for modulating cancer stem cells

Abstract

Disclosed are compositions and methods that use lysine demethylase inhibitors for inhibiting the growth of cancer stem cells or tumor initiating cells, for enhancing the biological effects of chemotherapeutic drugs or irradiation on cancer cells and/or for preventing cancer recurrence.

1 - 98 . (canceled) 
     
     
         99 . A method for treating or inhibiting the development of a metastatic cancer in a human subject, wherein the metastatic cancer comprises cancer stem cells (CSCs) and non-CSC tumor cells, wherein the CSCs express Sox2 mRNA or Sox2 polypeptide at a level that is less than ⅕ of the level of Sox2 mRNA or Sox2 polypeptide of a pluripotent stem cell, the method comprising concurrently administering to the subject a LSD inhibitor in an effective amount to inhibit formation, proliferation, survival, viability, maintenance or epithelial-to-mesenchymal transition (EMT) of the CSCs of the cancer or to stimulate mesenchymal-to-epithelial transition (MET) of the CSCs of the cancer, and a cancer therapy or agent that inhibits proliferation, survival or viability of the non-CSC tumor cells, to thereby treat or inhibit the development of the metastatic cancer. 
     
     
         100 . The method according to  claim 99 , wherein the LSD inhibitor is an LSD1 inhibitor. 
     
     
         101 . The method according to  claim 103 , wherein the LSD1 inhibitor is a selective LSD1 inhibitor. 
     
     
         102 . The method according to  claim 99 , wherein the LSD inhibitor is a Pan-LSD inhibitor. 
     
     
         103 . The method according to  claim 99 , wherein the cancer therapy or agent is selected from the group consisting of radiotherapy, surgery, chemotherapy, hormone ablation therapy, pro-apoptosis therapy, stem cell transplant and immunotherapy. 
     
     
         104 . The method according to  claim 99 , wherein the immunotherapy comprises antibody therapy. 
     
     
         105 . The method according to  claim 99 , wherein the cancer therapy or agent targets rapidly dividing cells or disrupts the cell cycle or cell division. 
     
     
         106 . The method according to  claim 99 , wherein the metastatic cancer is selected from metastatic breast cancer, metastatic prostate cancer, metastatic lung cancer, metastatic bladder cancer, metastatic pancreatic cancer, metastatic colon cancer, metastatic melanoma, metastatic liver cancer or metastatic glioma cancer. 
     
     
         107 . The method according to  claim 99 , wherein the metastatic cancer is metastatic breast cancer. 
     
     
         108 . The method according to  claim 99 , wherein the CSCs are capable of giving rise to non-CSC tumor cells that are hormone-resistant. 
     
     
         109 . The method according to  claim 99 , wherein the non-CSC tumor cells are hormone receptor negative for at least one hormone receptor selected from an estrogen receptor (ER) and a progesterone receptor (PR).