Methods for Treating Cancer with a WEE1 Inhibitor

Abstract

The present invention relates generally to the use of gene mutations, whose presence or absence are useful for predicting a patient's response to treatment with an anti-proliferative agent, in particular a WEE1 inhibitor. The presence or absence of a mutation to the TP53 gene, can be used to predict response to treatment with a WEE1 inhibitor in a patient presenting with a cancerous condition.

1 . A method of treating cancer in a patient comprising the steps of:
 1) selecting a patient diagnosed with cancer that has one or more TP53 gene mutations according to Table 3, or at least one basepair insertion or deletion in the TP53 gene that causes a frameshift in encoding the p53 protein resulting in loss of function, or a combination thereof in the cancer cell;   2) administering a therapeutically effective amount of a WEE1 inhibitor and optionally one or more additional anti-cancer agents to the patient.   
     
     
         2 . A method of treating cancer in a patient, in which the patient is diagnosed with cancer and has one or more TP53 gene mutations according to Table 3, or at least one basepair insertion or deletion in the TP53 gene that causes a frameshift in encoding the p53 protein resulting in loss of function, or a combination thereof in the cancer cell; comprising the step of administering a therapeutically effective amount of a WEE1 inhibitor and optionally one or more additional anti-cancer agents to the patient. 
     
     
         3 . A method of treating cancer in a patient, comprising the step of administering a therapeutically effective amount of a WEE1 inhibitor and optionally one or more additional anti-cancer agents to the patient, wherein the patient is diagnosed with cancer and has one or more TP53 gene mutations according to Table 3, or at least one basepair insertion or deletion in the TP53 gene that causes a frameshift in encoding the p53 protein resulting in loss of function, or a combination thereof in the cancer cell. 
     
     
         4 . The method of  claim 1 , wherein the TP53 gene mutation has an evidence score that is equal or greater than 2.5 according to Table 3. 
     
     
         5 . The method of  claim 1 , wherein the TP53 gene mutation has an evidence score that is equal or greater than 3 according to Table 3. 
     
     
         6 . The method of  claim 1 , wherein the TP53 gene mutation has an evidence score that is equal or greater than 3.5 according to Table 3. 
     
     
         7 . The method of  claim 1 , wherein the TP53 gene mutation has an evidence score that is equal or greater than 4.0 according to Table 3. 
     
     
         8 . The method of  claim 1 , wherein the TP53 gene mutation has an evidence score that is equal or greater than 4.5 according to Table 3. 
     
     
         9 . The method of  claim 1 , wherein the TP53 gene mutation has an evidence score that is equal to 5.0 according to Table 3. 
     
     
         10 . The method of  claim 1 , wherein the patient has at least one of the TP53 gene mutations resulting in the amino acid change selected from the group consisting of C238F, R248W and R273L according to Table 3, a stop codon at the codon encoding E298 in the p53 protein, or a deletion of a basepair in the codon encoding V157 in the p53 protein. 
     
     
         11 . The method of  claim 1 , wherein the WEE1 inhibitor is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 1 , wherein the WEE1 inhibitor is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 1 , wherein the cancer is selected from the group consisting of ovarian cancer, melanoma, lung cancer, colorectal cancer, colon cancer, rectum cancer, prostate cancer, and breast cancer. 
     
     
         14 . The method of  claim 1 , wherein the cancer is ovarian cancer. 
     
     
         15 . The method of  claim 1 , wherein the cancer is lung cancer. 
     
     
         16 . The method of  claim 1 , wherein the anti-cancer agent is selected from the group consisting of: 5-FU, carboplatin, doxorubicin, etoposide, gemcitabine, irinotecan, mitomycin, temozolomide and topotecan. 
     
     
         17 . The method of  claim 1 , wherein the anti-cancer agent is carboplatin and paclitaxel.