Methods and compositions for modulating cell proliferation and cell death

A method of inhibiting growth or proliferation of hyperproliferative cells in a subject, comprising:

• administering to the subject at least one cytotoxic agent and suramin in an amount that results in a plasma concentration of between 0.1 and 90 μg/ml which, together, is effective to inhibit growth or proliferation of the hyperproliferative cells, or is effective to induce death of the hyperproliferative cells.

A method of inhibiting growth or proliferation of, or inducing killing of tumor cells in a subject, comprising:

• administering to the subject at least one cytotoxic agent and suramin in an amount that results in a plasma concentration of between 0.1 and 90 μg/ml which, together, is effective to inhibit growth or proliferation of the tumor cells.

A method of inhibiting unwanted growth or proliferation of, or inducing killing of tumor cells in a human subject, comprising:

• administering to the human subject at least one cytotoxic agent and suramin in an amount that results in a plasma concentration of between 0.1 and 90 μg/ml, which together, is effective to reduce or inhibit the growth or proliferation of the established humor, induce cell death in the established tumors, or to reduce the size of the established tumors.

A method of inhibiting unwanted proliferation of, or inducing killing, of, an established tumor in a subject, comprising:

• administering to the subject at least one cytotoxic agent and suramin in an amount that results in a plasma concentration of between 0.1 and 90 μg/ml, which together, is effective to reduce or inhibit the growth or proliferation of the established tumor, induce cell death in the established tumors, or to reduce the size of the established tumors, wherein the established tumor is selected from the group consisting of lung carcinoma, renal cell carcinoma, glioma, melanoma, chemotherapy resistant tumors and metastatic tumors.

A method of inhibiting unwanted proliferation of, or inducing killing of, an established tumor in a subject, comprising:

• administering to the subject at least one cytotoxic agent and suramin in an amount that results in a plasma concentration of between 0.1 and 90 μg/ml, which together, is effective to reduce or Inhibit the growth or proliferation of the established lung tumor, induce cell death In the established lung tumors, or to reduce the size of the established lung tumors.

A method for inhibiting chemoresistance of a tumor cell to a cytotoxic agent, comprising:

• administering to the tumor cell suramin In an amount that results in a plasma concentration of between 0.1 end 90 μg/ml such that chemoresistance of the tumor cell to the cytotoxic agent is inhibited.

A method for treating or preventing a disorder involving aberrant growth or proliferation of benign proliferative tissue, comprising:

• contacting the tissue with at least one cytotoxic agent and suramin in an amount that results In a plasma concentration of between 0.1 and 90 μg/ml, which, together, is effective to Inhibit growth or proliferation of the tissue or to induce death of hyperproliferative cells.

A method of improving the efficacy of a cytotoxic agent, in a human subject, comprising:

• administering to the subject at least one cytotoxic agent;
• administering to the subject suramin in an amount that results in a plasma concentration of between 0.1 and 90 μg/ml,
• wherein the suramin enhances the efficacy of the cytotoxic agent, relative to the effect of the cytotoxic agent in the absence of the suramin.

A method of inhibiting growth or proliferation of hyperproliferative cells in a human subject, comprising:

• administering to the subject at least one cytoxic agent and suramin In an amount that results in a plasma concentration of between 0.1 and 90 μg/ml, which, together, is effective to inhibit growth or proliferation of the hyperproliferative cells, or is effective to induce death of the hyperproliferative cells.

A method of inhibiting growth or proliferation of, or inducing killing of tumor cells in a human subject, comprising:

• administering to the subject at least one cytotoxic agent and suramin in an amount that results in a plasma concentration of between 0.1 and 90 μg/ml, which, together, is effective to inhibit growth or proliferation of the tumor cells or Induce death of tumor cells.

A method of improving the efficacy of a cytotoxic agent, in a subject, comprising:

• administering to the subject at least one cytotoxic agent end administering to the subject suramin in an amount that results in a total exposure of not more than about 2,000 μm-day over 20 days,
• wherein the suramin enhances the efficacy of the cytotoxic agent, relative to the effect of the cytotoxic agent In the absence of the suramin.