Combination for use in treating diseases or conditions associated with melanoma, or treating diseases or conditions associated with activated B-raf pathway
The invention relates to the therapeutic use of a combination in a disease and condition associated with melanoma or a disease or a condition associated with activated BRAF pathway.
1. A synergistic combination of at least two compounds, at least one compound being taken from the first list and at least one compound being taken from the second list:
a) at least one of a miRNA-3157-5p, miRNA-10b-3p, miRNA-129-5p, miRNA-96-5p, miRNA-200c-5p, miRNA-182-3p, miRNA-16-5p, miRNA-497-5p, miRNA-518b and/or a miRNA-7-5p molecule, an equivalent or a precursor thereof, or a composition comprising said at least one miRNA, equivalent or precursor thereof, and
b) at least one B-raf and/or MEK inhibitor, or a composition comprising said at least one B-raf and/or MEK inhibitor, wherein the combination provides for a synergistic effect on inhibition of the proliferation of melanoma cells or cells harboring an activated B-raf pathway that are resistant to said B-raf and/or MEK inhibitor.
2. The combination according to claim 1 , wherein said at least one B-raf inhibitor is vemurafenib or dabrafenib, and/or wherein said at least one MEK inhibitor is trametinib or selumetinib.
3. The combination according to claim 1 , wherein:
a) said at least one compound from the first list is a miRNA-3157-5p, and/or an equivalent and/or a precursor thereof or a composition comprising said miRNA-3157-5p, and/or an equivalent and/or a precursor thereof and
b) said at least one compound from the second list is at least one B-raf and/or MEK inhibitor.
4. The combination according to claim 1 , further comprising another miRNA molecule, equivalent or precursor thereof, or a composition comprising said miRNA molecule, and/or an equivalent and/or a precursor thereof selected from:
a) at least one of miRNA-13, Let-7 and Let-7a and/or an equivalent or a precursor thereof and/or,
b) at least one antagomir of miRNA-221 and miRNA-222 and/or an equivalent or a precursor thereof.
5. The combination according to claim 1 , wherein said at least one compound from the first list and said at least one compound from the second list are:
(i) combined in a single composition; or
(ii) present in a kit of parts comprising at least two separate compositions for sequential or simultaneous administration to a subject.
6. A method for inhibiting growth and/or reducing viability of melanoma cells or of cells containing an activating BRAF mutation by administering a synergistic combination as defined in claim 1 to a subject in need thereof.
7. The method according to claim 6 , wherein sensitization of the subject to a B-raf and/or MEK inhibitor is promoted.
8. The combination according to claim 3 , wherein said at least one B-raf inhibitor is vemurafenib or dabrafenib, and/or wherein said at least one MEK inhibitor is trametinib or selumetinib.
9. The combination according to claim 1 , wherein the combination provides for a synergistic effect on inhibition of the proliferation of melanoma cells resistant to vemurafenib.
10. The combination according to claim 3 , wherein said at least one compound from the second list is vemurafenib.