Cancer combination therapies utilizing a nicotinamide phosphoribosyltransferase inhibitor in combination with a nicotinamide adenine dinucleotide salvage pathway precursor
AssigneeFred Hutchinson Cancer Research Center
InventorsDavid Hockenbery, Patrick Paddison
Life of this patent
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Abstract
Cancer combination therapies utilizing a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor in combination with a nicotinamide adenine dinucleotide (NAD) salvage pathway precursor are described. Cancers treated with the combination therapies can be nicotinamide riboside kinase (NMRK1) low cancers and/or Myc high cancers and can include various forms of glioblastomas.
Claims56
A method of treating a nicotinamide riboside kinase (NMRK)low cancer in a subject in need thereof comprising administering a therapeutically effective amount of (i) FK866 ((E)-N-[4-(1-benzoyl-4-yl)-butyl]-3-(pyridin-3-yl) acrylamide) and (ii) nicotinamide mononucleotide (NMN) and/or nicotinamide riboside (NR) to the subject thereby treating cancer in need the subject.
A method of treating cancer in a subject in need thereof comprising administering a therapeutically effective amount of a nicotinamide phosphoribosyltransferase (NAMPT) inhibitor and an external factor to a subject thereby treating cancer in need the subject.
A combination therapy for treating cancer comprising an NAM PT inhibitor and an external factor.
A method comprising:
- Incubating a population of NMRKlow cells and a population of NMRK+ cells with a test compound;
- Assessing the population of NMRKlow cells and the population of NMRK+ cells for cytotoxicity based on exposure to the test compound;
- If cytoxicity is observed in both populations, incubating a second population of NMRKlow cells and a second population of NMRK+ cells with the test compound and an external factor;
- Assessing the second population of NMRKlow cells and the second population of NMRK+ cells for cytotoxicity based on exposure to the test compound and the external factor;
- Identifying the test compound as a candidate for drug development if cytoxicity in the presence of the external factor is reduced in the NMRK+ cells but not the NMRKlow cells.
Use of NMKR1 status as a biomarker to select a cancer treatment for a subject.
A method comprising:
- Obtaining a cancer sample derived from a subject;
- Assessing the cancer sample for an expression level of NM KR and/or Myc;
- Treating the subject with a therapeutically effective amount of a NAMPT inhibitor and an external factor if the assessment reveals an NMRKlow and/or a Mychigh cancer.
Use of an expression change of a NAD pathway gene as a biomarker to select a cancer treatment for a subject.
Dependencies are inferred from the claim text.