Novel compositions of combinations of non-covalent dna binding agents and anti-cancer and/or anti-inflammatory agents and their use in disease treatment

Abstract

The invention provides for compositions for treating a cancer or an inflammatory disorder comprising a combination of agents in a pharmaceutically acceptable carrier, wherein said agents comprise: (i) a non-covalent DNA binding agent; and (ii) an anti-cancer or anti-inflammatory agent.

1 .- 43 . (canceled) 
     
     
         44 . A method of treating a subject with cancer or inflammation, comprising:
 a. identifying a subject in need of treatment;   b. administering to said subject a therapeutically effective amount of one or more of (a) a non-covalent DNA binding agent and (b) an anti-cancer agent or an anti-inflammatory agent;   
       wherein following said administration, there is inhibition of growth of a cancer cell or inflammation. 
     
     
         45 . The method of  claim 44 , wherein said identification step comprises determining whether said patient has a mutation in one or more genes and/or the gene pathway selected from the group consisting of: PTEN, p53, BRCA1, BRCA2, MLH1, PMS1, PMS2, MSH2, MSH6, REV3, XRCC1, XRCC2, XRCC3, RAD51, RAD52, REV, ATM, ATR, K-Ras, BRAF and the MRE1/RPA1/RAD51 complex. 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 44 , wherein said subject has a loss of function of at least one tumor suppressor gene. 
     
     
         48 . The method of  claim 47 , wherein said at least one tumor suppressor gene and/or the gene pathway is selected from the group consisting of: PTEN, p53, BRCA1, BRCA2, MLH1, PMS1, PMS2, MSH2, MSH6, REV3, XRCC1, XRCC2, XRCC3, RAD51, RAD52, REV, ATM, ATR, K-Ras, BRAF and the MRE1/RPA1/RAD51 complex. 
     
     
         49 . The method of  claim 44 , wherein said subject has a DNA mismatch repair deficiency. 
     
     
         50 . The method of  claim 44 , wherein said subject does not have a DNA mismatch repair deficiency. 
     
     
         51 . The method of  claim 44 , wherein said cancer is mutant K-ras positive or has other mutations in oncogenes and/or the oncogene pathway, conferring “gain of function”. 
     
     
         52 . The method of  claim 44 , wherein said cancer is wild-type and/or mutant K-ras or BRAF gene and/or the wild-type or mutant K-ras or BRAF gene pathway, and as such genes or gene pathways in the epidermal growth factor receptor (EGFR) signaling pathway. 
     
     
         53 . The method of  claim 44 , wherein said identification step comprises determining the response of a patient to a therapy for treating cancer. 
     
     
         54 . The method of  claim 44 , wherein said identification step is reported to said subject and/or a health care professional. 
     
     
         55 . The method of  claim 44 , wherein said non-covalent DNA binding agent binds to the minor groove of DNA. 
     
     
         56 . The method of  claim 44 , wherein said non-covalent DNA binding agent binds to a GC rich region of the minor groove. 
     
     
         57 . The method of  claim 44 , wherein said subject has a mutation in one or more genes and/or the gene pathway selected from the group consisting of: PTEN, p53, BRCA1, BRCA2, MLH1, PMS1, PMS2, MSH2, MSH6, REV3, XRCC1, XRCC2, XRCC3, RAD51, RAD52, REV, ATM, ATR, K-Ras, BRAF and the MRE1/RPA1/RAD51 complex. 
     
     
         58 . (canceled) 
     
     
         59 . The method of  claim 44 , wherein said cancer is selected from the group consisting of: lung cancer, breast cancer, osteosarcoma, neuroblastoma, colon adenocarcinoma, chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), acute promyelocytic leukemia (APL), sarcoma, myxoma, rhabdomyoma, fibroma, lipoma, teratoma; bronchogenic carcinoma, alveolar carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, mesothelioma, esophageal cancer, stomach cancer, pancreatic cancer, small bowel cancer, large bowel cancer; kidney cancer, bladder cancer, urethra cancer, prostate cancer, testis cancer; hepatoma, cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma, osteogenic sarcoma, fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma, multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma, benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma, giant cell tumors, cancer of the skull, meninges cancer, brain cancer, spinal cord cancer, uterus cancer, cervical cancer, cancer of the ovaries, vulva cancer, vagina cancer, Hodgkin's disease, non-Hodgkin's lymphoma, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karposi's sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma. 
     
     
         60 . The method of  claim 44 , wherein said cancer is triple negative breast cancer which is negative for the estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (HER2) receptors. 
     
     
         61 . The method of  claim 44 , wherein said cancer is MMR-deficient colorectal cancer. 
     
     
         62 . The method of  claim 44 , wherein said cancer is glioblastoma. 
     
     
         63 . (canceled) 
     
     
         64 . The method of  claim 44 , wherein the said cancer is non-small cell lung cancer. 
     
     
         65 .- 70 . (canceled) 
     
     
         71 . The method of  claim 44 , wherein said subject is a mammal. 
     
     
         72 . The method of  claim 44 , wherein said subject is a human. 
     
     
         73 .- 164 . (canceled)