Use of a combination of Dbait molecule and PARP inhibitors to treat cancer
The present invention relates to the combination of a PARP inhibitor with a Dbait molecule for treating cancer.
1. A pharmaceutical composition comprising a nucleic acid molecule and a poly(ADP-ribose)polymerase (PARP) inhibitor, wherein the nucleic acid molecule is a hairpin nucleic acid with a double-stranded DNA stem and a loop and has the following formula:
wherein C is a cholesteryl, Lm is a carboxamido tetraethylene glycol linker, p is 1 and L′ is 1,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane.
2. The pharmaceutical composition according to claim 1 , wherein the nucleic acid molecule is:
3. The pharmaceutical composition according to claim 1 , wherein the PARP inhibitor is selected from the group consisting of rucaparib (AG014699, PF-01367338), olaparib (AZD2281), veliparib (ABT888), iniparib (BSI 201), niraparib (MK 4827), talazoparib (BMN673), AZD 2461, CEP 9722, E7016, INO-1001, LT-673, MP-124, NMS-P118, XAV939, analogs, derivatives or a mixture thereof.
4. The pharmaceutical composition according to claim 1 , wherein the PARP inhibitor is selected from the group consisting of AZD2281 (Olaparib), ABT888 (Veliparib), BMN673, BSI-21 (Iniparib), AZD 2461, MK-4827 (Niraparib), and AG 014699 (Rucaparib).
5. A method of treating cancer which is not deficient or impaired for the homologous recombination repair, comprising the administration of the pharmaceutical composition according to claim 1 to a subject in need thereof.
6. The method according to claim 5 , wherein the cancer is selected from leukemia, lymphoma, sarcoma, melanoma, and cancers of the head and neck, kidney, ovary, pancreas, prostate, thyroid, lung, esophagus, breast, bladder, brain, colorectum, liver, and cervix.
7. The method according to claim 5 , wherein the PARP inhibitor is used at a sub-therapeutic amount.
8. The method according to claim 5 , wherein the PARP inhibitor and the DBait nucleic acid molecule are used in combination with radiotherapy and/or an antitumor chemotherapy with a DNA damaging agent.
9. A kit comprising a PARP inhibitor and a nucleic acid molecule, wherein the nucleic acid molecule is a hairpin nucleic acid with a double-stranded DNA stem and a loop and has the following formula:
wherein C is a cholesteryl, Lm is a carboxamido tetraethylene glycol linker, p is 1 and L′ is 1,19-bis(phospho)-8-hydraza-2-hydroxy-4-oxa-9-oxo-nonadecane.
10. The kit according to claim 9 , wherein the nucleic acid molecule is:
11. The kit according to claim 9 , wherein the PARP inhibitor is selected from the group consisting of rucaparib (AG014699, PF-01367338), olaparib (AZD2281), veliparib (ABT888), iniparib (BSI 201), niraparib (MK 4827), talazoparib (BMN673), AZD 2461, CEP 9722, E7016, INO-1001, LT-673, MP-124, NMS-P118, XAV939, analogs, derivatives or a mixture thereof.
12. The kit according to claim 10 , wherein the PARP inhibitor is selected from the group consisting of rucaparib (AG014699, PF-01367338), olaparib (AZD2281), veliparib (ABT888), iniparib (BSI 201), niraparib (MK 4827), talazoparib (BMN673), AZD 2461, CEP 9722, E7016, INO-1001, LT-673, MP-124, NMS-P118, XAV939, analogs, derivatives or a mixture thereof.
13. The kit according to claim 9 , wherein the PARP inhibitor is selected from the group consisting of AZD2281 (Olaparib), ABT888 (Veliparib), BMN673, BSI-21 (Iniparib), AZD 2461, MK-4827 (Niraparib), and AG 014699 (Rucaparib).
14. The kit according to claim 10 , wherein the PARP inhibitor is selected from the group consisting of AZD2281 (Olaparib), ABT888 (Veliparib), BMN673, BSI-21 (Iniparib), AZD 2461, MK-4827 (Niraparib), and AG 014699 (Rucaparib).
15. The pharmaceutical composition according to claim 2 , wherein the PARP inhibitor is selected from the group consisting of rucaparib (AG014699, PF-01367338), olaparib (AZD2281), veliparib (ABT888), iniparib (BSI 201), niraparib (MK 4827), talazoparib (BMN673), AZD 2461, CEP 9722, E7016, INO-1001, LT-673, MP-124, NMS-P118, XAV939, analogs, derivatives or a mixture thereof.
16. The pharmaceutical composition according to claim 2 , wherein the PARP inhibitor is selected from the group consisting of AZD2281 (Olaparib), ABT888 (Veliparib), BMN673, BSI-21 (Iniparib), AZD 2461, MK-4827 (Niraparib), and AG 014699 (Rucaparib).