Cancer therapy
A method of treating haematological cancer with a therapy comprising a DHODH inhibitor. Also provided is a combination therapy comprising a pan-HER inhibitor and a DHODH inhibitor for treating a haematological cancer.
1. A method of treating a haematological cancer, comprising administering a DHODH inhibitor 2-(3,5-difluoro-3′methoxybiphenyl-4-ylamino)nicotinic acid or a pharmaceutically acceptable salt thereof to a patient in need thereof, wherein the cancer is acute myeloid leukaemia (AML) excluding acute promyelocytic leukaemia.
2. A method of treatment according to claim 1 , wherein the DHODH inhibitor is employed in a combination therapy with a second therapy, wherein the second therapy is selected from an inhibitor of DNA repair, a PARP-1 inhibitor, a PARP-2 inhibitor, a topoisomerase I and/or a topoisomerase II inhibitor.
3. A method of treatment according to claim 2 , wherein the second therapy is an inhibitor of DNA repair, wherein the inhibitor is selected from TRC102, (2E)-2-[(4,5-Dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)methylene]-undecanoic acid [also known as E3330], NCS-666715 and NSC-124854, 8-oxoguamine, tanespirmycin, luminespib, alvespimycin, genetespib, retaspimycin, 6-Amino-8-[(6-iodo-1,3-benzodioxol-5-yl)thio]-N-(1-methylethyl)-9H-purine-9-propanamine (PU-H71), 4-[2-carbamoyl-5-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]anilino]cyclohexyl] 2-aminoacetate (SNX-5422), luminespib (resorcyinylic), 2-(2-ethyl-3,5-dihydroxy-6-(3-methoxy-4-(2-morpholinoethoxy)benzoyl)phenyl)-N,N-bis(2-methoxyethyl)acetamide (KW-2478), AT13387, 5,6-bis((E)-benzylideneamino)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (SCR7), 7-hydroxystaurosporine [UCN-01], trabectedin, MC113E, NER101 and combinations of two or more of the same.
4. A method of treatment according to claim 3 , wherein the inhibitor mechanism is via the base excision repair pathway.
5. A method of treatment according to claim 3 , wherein the inhibitor's target is independently selected from APE1, Pol β, FEN1, and PARP.
6. A method of treatment according to claim 2 , wherein the second therapy is a PARP inhibitor independently selected from olaparib, rucaparib, niraparib, iniparib, talazoparib, veliparib, CEP9722, E7016, BGB-290, AZD-2461, 3-aminobenzamide and combinations thereof.
7. A method of treatment according to claim 3 , wherein the inhibitor mechanism is via the mismatch repair pathway.
8. A method of treatment according to claim 3 , wherein the inhibitor mechanism is via the nucleotide excision pathway.
9. A method of treatment according to claim 3 , wherein the inhibitor is independently selected from 7-hydroxystaurosporine [UCN-01], trabectedin, MC113E, NER101 and combinations of two or more of the same.
10. A method of treatment according to claim 3 , wherein the inhibitor mechanism is via the double stranded break repair pathway.
11. A method of treatment according to claim 3 , wherein the inhibitor mechanism is via the non-homologous end joining pathway.
12. A method of treatment according to claim 3 , wherein the inhibitor is via the homologous recombination pathway.
13. A method of treatment according to claim 2 , wherein the therapy is a topoisomerase inhibitor independently selected from irinotecan, topotecan, camptothecin, lamellarin D, etoposide (VP-16), teniposide, doxorubicin, daunorubicin, mitoxantrone, amsacrine, ellipticines, aurintricarboxylic acid, 3-Hydroxy-2-[(1R)-6-isopropenyl-3-methyl-cyclohex-2-en-1-yl]-5-pentyl-1,4-benzoquinone (HU-331) and combinations thereof.