Methods for identifying therapeutic targets and treating and monitoring cancers

Abstract

The present invention provides methods for treating cancers having a mutation in one or more tumor suppressor genes, comprising providing to a subject in need thereof an inhibitor of a kinase, as well as related methods and compositions.

1 . A method for treating or preventing a cancer in a subject in need thereof, wherein the cancer comprises a mutation in a tumor suppressor gene, the method comprising providing to the subject an inhibitor of a kinase selected from NEK4, TRIB2, TXK, CAMK2B, NUAK2, EPHA3, ALK, PIP5K1B, RPS6KL1, FGFR3, WEE1, and PRKCE. 
     
     
         2 . The method of  claim 1 , wherein the tumor suppressor gene is a DNA-PKcs, Atm, p19 Arf , p53, Hras, Kras or Prkdc gene, or wherein the cancer comprises a mutation in both a p53 tumor suppressor gene and one or more of a Hras or Kras gene. 
     
     
         3 .- 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the cancer is a primary tumor. 
     
     
         13 . The method of  claim 1 , wherein the cancer is a recurrent or metastatic tumor. 
     
     
         14 .- 15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the kinase is WEE1, and the subject is further provided with cisplatin. 
     
     
         17 . The method of  claim 1 , further comprising determining a level of expression or activity of the kinase or the gene encoding the kinase in cancer cells obtained from the subject. 
     
     
         18 . The method of  claim 17 , wherein the level of expression or activity of the kinase gene or its encoded gene product is determined prior to providing the subject with the inhibitor. 
     
     
         19 . A method of monitoring the progression or regression of a tumor in response to a treatment, comprising:
 (a) determining a level of expression or activity of a kinase gene or its encoded gene product in cancer cells obtained from the subject prior to or at about the same time as providing the subject with the inhibitor; and   (b) determining a level of expression or activity of the kinase gene or its encoded gene product in cancer cells obtained from the subject following a time period after providing the subject with the inhibitor;   
       wherein a reduced level of expression or activity determined for (b) as compared to the level of expression or activity determined for (a) indicates that the treatment is effective, and wherein the kinase is NEK4, TRIB2, TXK, CAMK2B, NUAK2, EPHA3, ALK, PIP5K1B, RPS6KL1, FGFR3, WEE1, or PRKCE. 
     
     
         20 . A method of identifying a therapeutic drug target in a diseased cell, comprising:
 (a) screening a plurality of siRNAs for their ability to inhibit growth or reduce viability of a human diseased cell or a human cell having a defined mutation;   (b) identifying one or more genes targeted by one or more siRNAs of (a) that inhibit growth or reduce viability of the human cell;   (c) screening a plurality of siRNAs for their ability to inhibit growth or reduce viability of a non-human diseased cell or a non-human cell having a defined mutation;   (d) identifying one or more genes targeted by one or more siRNAs of (c) that inhibit growth or reduce viability of the non-human cell; and   (e) determining one or more genes identified according to both (b) and (d),   
       wherein the human diseased cell and the non-human disease cell share the same disease or the mutation in the human cell is in the same gene as the mutation in the non-human cell, and wherein the one or more genes determined according to (e) or their encoded products are identified as therapeutic drug targets. 
     
     
         21 .- 32 . (canceled)