Compositions and methods for cancer expressing pde3a or slfn12

Abstract

The present invention features improved methods of identifying patients having cancer (e.g., melanoma, adenocarcinoma, lung, cervical, liver or breast cancer) using biomarkers (e.g., PDE3A, SLFN12) that correlate with drug sensitivity and consequently treating a stratified patient population with an agent of the invention (e.g., DNMDP, zardaverine, and anagrelide).

1 - 3 . (canceled) 
     
     
         4 . A method of identifying a subject having a cancer cell responsive to PDE3A modulation, the method comprising detecting an increase in a PDE3A and/or SLFN12 polypeptide or polynucleotide level in a biological sample of the subject relative to a reference, thereby identifying said subject as having a cancer responsive to PDE3A modulation. 
     
     
         5 . A method of identifying a subject having a cancer that is resistant to PDE3A modulation, the method comprising detecting a decrease in the level of a SLFN12 polypeptide or polynucleotide level in a biological sample of the subject relative to a reference, thereby identifying said subject as having a cancer resistant to PDE3A modulation. 
     
     
         6 . The method of  claim 4 , wherein the level of PDE3A or SLFN12 is detected by a method selected from the group consisting of immunoblotting, mass spectrometry, and immunoprecipitation. 
     
     
         7 . The method of  claim 4 , wherein the level of PDE3A or SLFN12 polynucleotide is detected by a method selected from the group consisting of quantitative PCR, Northern Blot, microarray, mass spectrometry, and in situ hybridization. 
     
     
         8 . The method of  claim 4 , wherein the cancer cell is a melanoma, endometrium, lung, hematopoetic/lymphoid, ovarian, cervical, soft-tissue sarcoma, leiomyosarcoma, urinary tract, pancreas, thyroid, kidney, glioblastoma, or breast cancer cell. 
     
     
         9 . The method of  claim 4 , wherein the cancer cell is not a B-cell proliferative type cancer. 
     
     
         10 . The method of  claim 4 , wherein the cancer cell is not multiple myeloma. 
     
     
         11 - 13 . (canceled) 
     
     
         14 . The method of  claim 4 , wherein the biological sample is a tissue sample comprising a cancer cell. 
     
     
         15 . A kit for identifying a subject having cancer responsive to PDE3A modulation, the kit comprising a first capture reagent that binds a PDE3A polypeptide or polynucleotide and a second capture reagent that binds SLFN12 polypeptide or polynucleotide. 
     
     
         16 . A kit for decreasing cancer cell proliferation in a subject pre-selected as responsive to a PDE3A modulator, the kit comprising an effective amount of DNMDP, zardaverine, and/or anagrelide, or a pharmaceutically acceptable salt thereof. 
     
     
         17 - 18 . (canceled)