p53 Inhibitors and Therapeutic Use of the Same

Abstract

The therapeutic use of temporary p53 inhibitors in the treatment of p53-mediated diseases, conditions, and injuries is disclosed.

1 . A method of treating a disease or condition wherein inhibition of p53 activity provides a benefit comprising administering a therapeutically effective amount of a temporary p53 inhibitor to an individual suffering from the disease or condition. 
     
     
         2 . The method of  claim 1  wherein the disease or condition comprises a p53-deficient cancerous tumor. 
     
     
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         22 . A method of reducing or eliminating normal cell death attributable to a treatment of a disease or condition comprising administering a therapeutically effective amount of a temporary p53 inhibitor to a mammal to reversibly inhibit p53 activity. 
     
     
         23 . The method of  claim 22  wherein the disease or condition is a cancer, hyperthermia, hypoxia, stroke, ischemia, acute inflammation, a burn, or cell aging. 
     
     
         24 . The method of  claim 23  wherein the disease is a cancer comprising a tumor that lacks functional p53. 
     
     
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         26 . A method of reducing or eliminating damage to normal tissue attributable to a treatment for cancer comprising administering a therapeutically effective of a temporary p53 inhibitor to a mammal to reversibly inhibit p53 activity. 
     
     
         27 . The method of  claim 26  wherein the cancer treatment comprises chemotherapy. 
     
     
         28 . The method of  claim 26  wherein the cancer treatment comprises radiation therapy. 
     
     
         29 . A cancer treatment composition comprising:
 (a) a chemotherapeutic drug; and   (b) a temporary p53 inhibitor.   
     
     
         30 . An improved method of treating cancer comprising administration of a therapeutically effective radiation dose to a mammal to treat a cancer, and administration of a therapeutically effective amount of a temporary p53 inhibitor to the mammal to reversibly inhibit p53 activity. 
     
     
         31 . The method of  claim 30  wherein the radiation dose and p53 inhibitor are administered simultaneously. 
     
     
         32 . The method of  claim 30  wherein the p53 inhibitor is administered prior to administration of the radiation dose. 
     
     
         33 . A method of preventing cell death attributable to a stress-inducing event affecting the cell, said method comprising treating the cell with therapeutically effective of a compound of a temporary p53 inhibitor to reversibly inhibit p53 activity. 
     
     
         34 . The method of  claim 33  wherein the stress-inducing event comprises a cancer treatment, a trauma, hyperthermia, hypoxia, ischemia, stroke, a burn, a seizure, a tissue or organ prior to transplanting, preparing a host for a bone marrow transplant, or DNA damage. 
     
     
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         39 . A method of sensitizing p53-deficient cells to a cancer therapy comprising administering, in conjunction with the cancer therapy, a sufficient amount of a temporary p53 inhibitor to a mammal to destroy p53-deficient cells that survive in an absence of the p53 inhibitor. 
     
     
         40 . An improved method of treating cancer comprising administration of a therapeutically effective dose of a chemotherapeutic agent to a mammal to treat a cancer, and administration of a sufficient amount of a temporary p53 inhibitor to the mammal to reversibly inhibit p53 activity, wherein the dose of the chemotherapeutic agent is greater than a dose of the identical chemotherapeutic agent required to treat the cancer in the absence of administration of the p53 inhibitor. 
     
     
         41 . The method of  claim 40  wherein the mammal is free of a cancer induced by temporary p53 suppression. 
     
     
         42 . A method of reducing or eliminating p53-mediated side effects associated with a cancer therapy comprising administering a therapeutically effective dose of a temporary p53 inhibitor to a mammal in conjunction with the cancer therapy. 
     
     
         43 . The method of  claim 42  wherein the cancer therapy comprises radiation therapy. 
     
     
         44 . The method of  claim 42  wherein the cancer therapy comprises chemotherapy. 
     
     
         45 . The method of  claim 42  wherein the p53-mediated side effect comprises one or more of hair loss, testicular cell damage, intestinal epithelia cell damage, lymphoid system damage, or hemopoietic system damage.