Rational combination therapy for the treatment of cancer

摘要

The present disclosure provides methods of using inhibitors of chaperone proteins, such as HSP90 inhibitors, in combination with agents that increase protein toxic stress on tumor cells or agents that induce biochemical reconnection of chaperomes. The protein toxic agent is administered prior to the administration of the chaperone protein to achieve synergistic activity. Specifically, the inventors have shown that cancer cells are pre-formed with a reservoir of a pre-formed chaperome complex along with all its appendages (cochaperones and cofactors) in anticipation of increased activity in abnormal cells. ). In addition, the inventors also demonstrate that cancer cells that are biochemically reconnected to form these multiple chaperome clusters (epichaperomes) are dependent on the epichaperome for survival.