Use of VEGFR1 as a biomarker
The present invention is related to the use of VEGFR1 or of a nucleic acid coding for VEGFR1 as a biomarker in a method for the treatment of a subject, wherein the method for the treatment comprises administering to the subject a PKN3 inhibitor.
1. A method of treating a subject and determining the responsiveness of the subject to treatment with a protein kinase N beta (PKN3) inhibitor comprising:
determining the level of a VEGFR1 or of a nucleic acid coding for a VEGFR1 in a sample from the subject prior to the treatment of said subject,
administering a PKN3 inhibitor to said subject having a disease treatable with said PKN3 inhibitor;
determining the level of a VEGFR1 or of a nucleic acid coding for a VEGFR1 in a sample from the subject after the subject has been subjected to the method of treatment; and
identifying the subject as a responder to said treatment with said PKN3 inhibitor if the level of a VEGFR1 or a nucleic acid coding for a VEGFR1 in a sample from the subject after the subject having been subjected to the method of treatment is decreased compared to the level of a VEGFR1 or a nucleic acid coding for a VEGFR1 in a sample from the subject prior to the subject having being subjected to the method of treatment; and
administering said PKN3 inhibitor to a subject identified as a responder to said treatment.
2. The method according to claim 1 , wherein the decrease in level of the VEGFR1 or the nucleic acid coding for the VEGFR1 is a decrease of 10% or more, of 20% or more, 40% or more, 60% or more or 80% or more.
3. The method according to claim 1 , wherein the VEGFR1 is VEGFR1, VEGFR1 variant 2, VEGFR1 variant 1, VEGFR1 variant 3, VEGFR1 variant 4, soluble VEGFR1, or soluble VEGFR1 variant 2 or is a nucleic acid encoding VEGFR1, VEGFR1 variant 2, VEGFR1 variant 1, VEGFR1 variant 3, VEGFR1 variant 4, soluble VEGFR1, or soluble VEGFR1 variant 2.
4. The method according to claim 1 , wherein the PKN3 inhibitor is an siRNA as follows:
(SEQ ID NO: 11)
5′ 5u8u7c6g8a6g5c7u7a6g5c5 3′
(SEQ ID NO: 12)
3′ a6c6g8u7c5u7a8g6g5u7a8a 5′
with unmodified ribonucleotides being as indicated and modified ribonucleotides being represented as follows:
5: 2′-O-Methyl-u,
6: 2′-O-Methyl-a,
7: 2′-O-Methyl-c,
8: 2′-O-Methyl-g.