Manipulation of hairy and enhancer of split 3 (Hes3) and its regulators/mediators as an anti-cancer strategy

Patent metadata

Field	Value
Publication number	US-9943570-B2
Application number	US-201314653744-A
Country	US
Kind code	B2
Filing date	Dec 20, 2013
Priority date	Dec 21, 2012
Publication date	Apr 17, 2018
Grant date	Apr 17, 2018

Abstract

The present invention relates to an inhibitor of Hairy and Enhancer of Split 3 (Hes3) or for use in treating a tumor. The invention further relates to an in-vitro method for diagnosing a tumor, comprising determining the amount of Hes3 protein in a cerebrospinal fluid (CSF)-derived sample obtained from a subject, wherein an increased amount of Hes3 protein is indicative of the presence of a tumor.

First claim

The invention claimed is:

1. A method for treating a subject having a brain tumour, the method comprising:
determining the amount of Hes3 protein in a cerebrospinal fluid (CSF) sample obtained from the subject; and
administering to the subject an inhibitor of Hairy and Enhancer of Split 3 (Hes3) in a therapeutically effective amount to reduce the tumour burden or eradicate the tumour in the subject;
wherein the inhibitor comprises an anti-Hes3 siRNA.

2. The method according to claim 1 , wherein the amount of Hes3 is determined using an antibody and/or mass spectrometry.

3. The method according to claim 1 , wherein the amount of Hes3 protein positively correlates with the aggressiveness of the tumour.

4. The method according to claim 1 , wherein the subject is a human.

5. The method according to claim 1 , wherein the inhibitor reduces the number of or eliminates cancer stem cells (CSCs).

6. The method according to claim 1 , wherein the brain tumour comprises a glioma, a glioblastoma, a meningioma, a pituitary adenoma, a vestibular schwannoma, a primary CNS lymphoma, or a medulloblastoma.

7. The method according to claim 1 , wherein the inhibitor is administered in combination with a second therapeutic compound and/or radiation.

8. The method according to claim 7 , wherein the second compound is a chemotherapeutic compound.

9. The method of claim 1 , wherein the brain tumor comprises a primary brain tumor.

10. The method of claim 1 , wherein the brain tumor comprises a meningioma I.

11. The method of claim 1 , wherein the brain tumor comprises a glioblastoma multiforme grade IV.

12. The method according to claim 1 , wherein the anti-Hes3 siRNA is selected from the group consisting of sc88003, SR318208A, and SR318208C.

13. The method of claim 1 , wherein the Hes3 protein in the CSF sample comprises an increase of at least 1.5 fold the normal value.

Assignees

• Univ Dresden Tech
• Univ Dresden Tech

Inventors

• Androutsellis-Theotokis Andreas

Classifications

• C12N2310/16

  Aptamers · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K38/2278 Primary

  Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin) · CPC title

• C12N2310/12

  catalytic nucleic acids, e.g. ribozymes · CPC title

• A61N5/10

  X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) · CPC title