Enhancement of tumor response to chemotherapy by activation of the asmase/ceramide pathway through timed administration of a short-acting anti-angiogenic agent

A method for increasing the efficacy of a first and a second chemotherapeutic agent, comprising:

• a) administering a first treatment by contacting the first chemotherapeutic agent with tumor endothelial cells;
• b) administering a second treatment by contacting the tumor endothelial cells with the second chemotherapeutic agent within 120 hours of the first treatment;
• wherein the first and second chemotherapeutic agents are selected from the group consisting of a taxane, an alkylating agent, a topoisomerase inhibitor, an antimetabolite, and any combination thereof;
• wherein the tumor endothelial cells have a de-repressed ASMase at the time of the first and second treatments;
• and wherein administration of the first and second treatments results in greater level of apoptosis of the tumor endothelial cells compared to control tumor endothelial cells in which the ASMase is not de-repressed.

A method for increasing the efficacy of a first and a second chemotherapeutic agent, comprising:

• a) selecting tumor endothelial cells having a de-repressed ASMase;
• b) administering a first treatment by contacting the tumor endothelial cells with the first chemotherapeutic agent;
• c) administering a second treatment by contacting the tumor endothelial cells with the second chemotherapeutic agent within 120 hours of the first treatment;
• wherein the first and second chemotherapeutic agents are selected from the group consisting of a taxane, an alkylating agent, a topoisomerase inhibitor, an antimetabolite, and any combination thereof;
• wherein the tumor endothelial cells also have the de-repressed ASMase at the time of the second treatment;
• and wherein administration of the first and second treatments results in greater level of apoptosis of the tumor endothelial cells compared to control tumor endothelial cells in which the ASMase is not de-repressed.

A method for treating a tumor in a subject, comprising:

• a) administering a first treatment of a chemotherapeutic agent to a subject that has a tumor with a de-repressed ASMase;
• wherein the chemotherapeutic agent is selected from the group consisting of a taxane, an alkylating agent, a topoisomerase inhibitor, an antimetabolite, and any combination thereof;
• and
• wherein administration of the chemotherapeutic agent results in a reduction of tumor size greater than that of a control tumor in a subject in which the ASMase is not de-repressed.