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US 2022/0065865 A1Published application
Methods of treatment and diagnosis of tumours
OwnerDarrell GREEN, William FRASERinventors
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OwnerDarrell GREEN, William FRASERinventors
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The invention relates to a method of treating a cartilage matrix-forming bone tumour and/or a metastatic cancer originating from a cartilage matrix-forming bone tumour, for example chondrosarcoma, in which one or more of an inhibitor of RUNX2 activity, an inhibitor of RUNX2 expression, an inhibitor of YBX1 activity and an inhibitor of YBX1 expression, is administered to a subject in need thereof. The invention also relates to an in vitro method for detecting the presence of a cartilage matrix-forming bone tumour in a subject or the risk of a subject developing a cartilage matrix-forming bone tumour, for example chondrosarcoma, in which the following steps are performed: (i) measuring the expression level of at least one of RUNX2 and YBX1 in a biological sample obtained from a subject, and (ii) comparing the expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject with the respective expression level of RUNX2 and/or YBX1 in normal cartilage or other biological material. A higher expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject compared to the respective expression level of RUNX2 and/or YBX1 in the normal cartilage or other biological material indicates the presence of or an increased risk of developing a cartilage matrix-forming bone tumour.
A composition for use in a method of treating a cartilage matrix-forming bone tumour and/or a metastatic cancer originating from a cartilage matrix-forming bone tumour, wherein the composition comprises one or more of an inhibitor of RUNX2 activity, an inhibitor of RUNX2 expression, an inhibitor of YBX1 activity and an inhibitor of YBX1 expression.
The method or composition for use of any preceding claim, wherein the cartilage matrix-forming bone tumour is a cartilage matrix-forming bone cancer.
The method or composition for use of any preceding claim, wherein the cartilage matrix-forming bone tumour overexpresses RUNX2 and/or YBX1 in comparison to normal cartilage or other biological material.
The method or composition for use of any preceding claim, wherein the cartilage matrix-forming bone tumour is chondrosarcoma.
The method or composition for use of any preceding claim, wherein the inhibitor of RUNX2 activity and/or the inhibitor of YBX1 activity inhibits binding of RUNX2 and/or YBX1 to DNA and/or mRNA;
The method or composition for use of any preceding claim, wherein the inhibitor of RUNX2 activity and/or YBX1 activity inhibits interaction of YBX1 protein with RUNX2 transcripts and/or RUNX2 protein.
The method or composition for use of any preceding claim, wherein the inhibitor of RUNX2 activity or the inhibitor of RUNX2 expression is a compound according to formula (I) or a pharmaceutically acceptable salt, ester or prodrug thereof,
The method or composition for use of any preceding claim, wherein the inhibitor of YBX1 activity or the inhibitor of YBX1 expression is a small RNA molecule comprising a SCUBYC motif.
The method or composition for use of any preceding claim, wherein the inhibitor of YBX1 activity or the inhibitor of YBX1 expression is a tRNA derived fragment (tRF) or analogue thereof, for example tRF-Gly-TCC or an analogue thereof.
The method or composition for use of any preceding claim, wherein the inhibitor of RUNX2 expression and/or the inhibitor of YBX1 expression is a siRNA.
An in vitro method for detecting the presence of a cartilage matrix-forming bone tumour in a subject or the risk of a subject developing a cartilage matrix-forming bone tumour, the method comprising (i) measuring the expression level of at least one of RUNX2 and YBX1 in a biological sample obtained from a subject, and (ii) comparing the expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject with the respective expression level of RUNX2 and/or YBX1 in normal cartilage or other biological material, wherein a higher expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject compared to the respective expression level of RUNX2 and/or YBX1 in the normal cartilage or other biological material indicates the presence of or an increased risk of developing a cartilage matrix-forming bone tumour.
An in vitro method for determining the prognosis of a subject having a cartilage matrix-forming bone tumour, the method comprising (i) measuring the expression level of at least one of RUNX2 and YBX1 in a biological sample obtained from the subject, and (ii) comparing the expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject with the respective expression level of RUNX2 and/or YBX1 in normal cartilage or other biological material, wherein the subject's prognosis decreases with increasing expression level of RUNX2 and/or YBX1 in the biological sample obtained from the subject.
Dependencies are inferred from the claim text.