US2014227284A1PendingUtilityA1

Synthetic lethality and the treatment of cancer

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Individually held — no corporate assignee on recordPriority: Jul 22, 2011Filed: Jul 23, 2012Published: Aug 14, 2014
Est. expiryJul 22, 2031(~5 yrs left)· nominal 20-yr term from priority
Inventors:Luc G. BerthiaumeErwan BeauchampConganige Maneka Anne PerinpanayagamChuiyee Yap
A61P 43/00A61P 35/02A61P 35/00G01N 33/57595G01N 33/575C07K 16/40A61K 31/12A61K 31/191G01N 33/5091A61K 31/713C12Q 1/686A61K 45/06A61K 31/496A61K 31/28A61K 31/7105G01N 33/57557G01N 2800/52G01N 33/6893G01N 33/574
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Claims

Abstract

Described herein are compounds, compositions and methods for treatment of cancer. Also described are methods and uses for identifying subject with cancer that are suitable for treatment with the compounds, composition and methods are described herein. In one aspect of the present invention, there is provided a method of treating a subject having a cancer deficient in NMT2, comprising: administering to said subject an NMT inhibitor.

Claims

exact text as granted — not AI-modified
1 . A method of treating a subject having a cancer deficient in NMT2, comprising: administering to said subject an NMT inhibitor. 
     
     
         2 . The method of  claim 1 , wherein said NMT inhibitor is a NMT1 inhibitor. 
     
     
         3 . The method of  claim 2 , wherein said cancer is a lymphoma. 
     
     
         4 . The method of  claim 3 , wherein said lymphoma is a B cell lymphoma. 
     
     
         5 . The method of  claim 4 , wherein said B cell lymphoma is follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, B-CLL/SLL, immunocytoma/Waldenstrom's, MALT-type/monocytoid B cell lymphoma, Burkitt's lymphoma, a pediatric lymphoma, or anaplastic large cell lymphoma. 
     
     
         6 . The method of  claim 2 , where in said NMT inhibitor is a small molecule, an antibody, a peptide fragment, or a nucleic acid. 
     
     
         7 . The method of  claim 6 , wherein said small molecule is Tris-DBA, HMA, or DDD85646, or a derivative thereof. 
     
     
         8 . The method of  claim 6 , wherein said antibody is a monoclonal antibody or a polyclonal antibody. 
     
     
         9 . The method of  claim 6 , wherein said nucleic acid comprises a dsRNA molecule, a RNAi molecule, miRNA molecule, a ribozyme, a shRNA molecule, or a siRNA molecule. 
     
     
         10 . The method of  claim 1 , wherein said subject is a human subject. 
     
     
         11 . The method of  claim 1  further comprising administering a chemotherapeutic agent. 
     
     
         12 . The method of  claim 11 , wherein said chemotherapeutic agent is CHOP, GAP-BOP, m-BACOD, ProMACE-MOPP, ProMACE-CytaBOM, MACOP-B, IMVP-16, MIME, DHAP, ESHAP, CEFF(B), CAMP, VABCD, ABDIC, CBVD, PCVP, CEP, EVA, MOPLACE, MIME, MINE, MTX-CHOP, CEM, CEVD, CAVP, EVAP, or EPOCH. 
     
     
         13 . A method of treating a subject having cancer, comprising:
 a. measuring a sample from said subject to determine whether said sample is deficient in NMT2; and   b. administering an inhibitor of NMT to said subject when said sample is deficient in NMT2.   
     
     
         14 . The method of  claim 13 , wherein said NMT inhibitor is a NMT1 inhibitor. 
     
     
         15 . The method of  claim 14 , wherein said cancer is a lymphoma. 
     
     
         16 . The method of  claim 15 , wherein said lymphoma is a B cell lymphoma. 
     
     
         17 . The method of  claim 16 , wherein said B cell lymphoma is follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, B-CLL/SLL, immunocytoma/Waldenstrom's, MALT-type/monocytoid B cell lymphoma, Burkitt's lymphoma, a pediatric lymphoma, or anaplastic large cell lymphoma. 
     
     
         18 . The method of  claim 14 , where in said NMT inhibitor is a small molecule, an antibody, a peptide fragment, or a nucleic acid. 
     
     
         19 . The method of  claim 18 , wherein said small molecule is Tris-DBA, HMA, or DDD85646, or a derivative thereof. 
     
     
         20 . The method of  claim 18 , wherein said antibody is a monoclonal antibody or a polyclonal antibody. 
     
     
         21 . The method of  claim 18 , wherein said nucleic acid comprises a dsRNA molecule, a RNAi molecule, miRNA molecule, a ribozyme, a shRNA molecule, or a siRNA molecule. 
     
     
         22 . The method of  claim 13 , wherein said subject is a human subject. 
     
     
         23 . The method of  claim 13  further comprising administering a chemotherapeutic agent. 
     
     
         24 . The method of  claim 23 , wherein said chemotherapeutic agent is CHOP, GAP-BOP, m-BACOD, ProMACE-MOPP, ProMACE-CytaBOM, MACOP-B, IMVP-16, MIME, DHAP, ESHAP, CEFF(B), CAMP, VABCD, ABDIC, CBVD, PCVP, CEP, EVA, MOPLACE, MIME, MINE, MTX-CHOP, CEM, CEVD, CAVP, EVAP, or EPOCH. 
     
     
         25 . The method of  claim 13 , wherein measuring of said sample is carried out using quantitative fluorescence activated cell sorting, enzyme linked immunosorbent assay, immunohistochemistry, quantitative immunohistochemistry, fluorescence resonance energy transfer, Forster resonance energy transfer, biomolecular fluorescence complementation, mass spectrometry, immunoblot assay or coimmunoprecipitation assay. 
     
     
         26 . A kit for treating cancer in of treating a subject having a cancer deficient in NMT2, comprising: an NMT inhibitor; and instructions for the use thereof. 
     
     
         27 . The kit of  claim 26 , wherein said NMT inhibitor is a NMT1 inhibitor. 
     
     
         28 . The kit of  claim 27 , wherein said cancer is a lymphoma. 
     
     
         29 . The kit of  claim 28 , wherein said lymphoma is a B cell lymphoma. 
     
     
         30 . The kit of  claim 29  wherein said B cell lymphoma is follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, B-CLL/SLL, immunocytoma/Waldenstrom's, MALT-type/monocytoid B cell lymphoma, Burkitt's lymphoma, a pediatric lymphoma, or anaplastic large cell lymphoma. 
     
     
         31 . The kit of  claim 26 , where in said NMT inhibitor is a small molecule, an antibody, a peptide fragment, or a nucleic acid. 
     
     
         32 . The kit of  claim 31 , wherein said small molecule is Tris-DBA, HMA, or DDD85646, or a derivative thereof. 
     
     
         33 . The kit of  claim 31 , wherein said antibody is a monoclonal antibody or a polyclonal antibody. 
     
     
         34 . The kit of  claim 31 , wherein said nucleic acid comprises a dsRNA molecule, a RNAi molecule, miRNA molecule, a ribozyme, a shRNA molecule, or a siRNA molecule. 
     
     
         35 . The kit of  claim 26 , wherein said subject is a human subject. 
     
     
         36 . The kit of  claim 26 , further comprising a chemotherapeutic agent. 
     
     
         37 . The kit of  claim 36 , wherein said chemotherapeutic agent is CHOP, GAP-BOP, m-BACOD, ProMACE-MOPP, ProMACE-CytaBOM, MACOP-B, IMVP-16, MIME, DHAP, ESHAP, CEFF(B), CAMP, VABCD, ABDIC, CBVD, PCVP, CEP, EVA, MOPLACE, MIME, MINE, MTX-CHOP, CEM, CEVD, CAVP, EVAP, or EPOCH. 
     
     
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         62 . A method of using NMT2 as a marker for one or more of diagnosis, prognosis, classifying, or monitoring of cancer in a subject. 
     
     
         63 . A method of using protein myristoylation as a marker for one or more of diagnosis, prognosis, classifying or monitoring cancer in a subject. 
     
     
         64 . A method of using protein acylation as a marker for one or more of diagnosis, prognosis, classifying or monitoring cancer in a subject. 
     
     
         65 . The method of  claim 62 , wherein said cancer is lymphoma. 
     
     
         66 . The method of  claim 64 , wherein said lymphoma is B cell lymphoma. 
     
     
         67 . The method of  claim 66 , B cell lymphoma is follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, B-CLL/SLL, immunocytoma/Waldenstrom's, MALT-type/monocytoid B cell lymphoma, Burkitt's lymphoma, a pediatric lymphoma, or anaplastic large cell lymphoma. 
     
     
         68 . The method of  claim 62 , wherein said marker is measured using an assay selected from immunoassays or nucleic acid detection, or protein activity.

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