Direct and selective inhibition of MDM4 for treatment of cancer
AssigneesVib Vzw, Katholieke Universiteit Leuven, K.U.Leuven R&D, Agency for Science, Technology and Research
InventorsJean-Christophe Marine, Ernesto Guccione, Marco Bezzi
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Abstract
The present application relates to the field of cancer, particularly that of cancers with high MDM4 protein levels (such as melanoma, breast, colon or lung cancers, glioblastoma, retinoblastoma, etc.). It is shown herein that direct and selective inhibition of MDM4, e.g., by antisense RNA, leads to growth inhibition of cancer cells and sensitization to chemo or targeted therapies. Also provided are simple ways of determining which patients are most amenable for such treatment by comparing specific transcript levels.
Claims18
A method of treating a subject having a tumor with an inhibitor of MDM4, the method comprising:
- determining, in the tumor, or in a sample from the tumor, that the ratio of MDM4 full-length RNA transcript to MDM4 transcript lacking exon 6 is higher than 1;
- and
- administering the inhibitor of MDM4 to the subject;
- wherein the inhibitor of MDM4 induces exon 6 skipping in MDM4 mRNA.
A method of treating a subject having a tumor with an inhibitor of MDM4, the method comprising:
- determining, in the tumor, or in a sample from the tumor, that the ratio of MDM4 full-length RNA transcript to the sum of MDM4 transcript lacking exon 6 and MDM4 full-length RNA transcript is higher than 0.4;
- and
- administering the inhibitor of MDM4 to the subject;
- wherein the inhibitor of MDM4 induces exon 6 skipping in MDM4 mRNA.
A method of treating a patient having a tumor comprising administering to the patient an antisense oligonucleotide directed to MDM4 RNA that induces skipping of exon 6 in MDM4 RNA, thereby inducing skipping of exon 6 in MDM4 RNA in a tumor of the patient.
Dependencies are inferred from the claim text.