Compositions and methods for inhibition and targeting of p97
AssigneeCalifornia Institute of Technology
InventorsTsui-Fen Chou, Shan Li, Feng Wang, Nadia Houerbi
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Abstract
Provided herein are methods and compositions for inhibiting p97, for the treatment of a cancer in a subject, or a symptom thereof. Upon treatment, the cancer, or a symptom thereof is reduced in the subject. Additionally, methods for measuring sensitivity of a subject to p97 inhibition, methods of assessing a pharmaceutical agent for p97 inhibition activity, and methods of assessing the effect of a pharmaceutical agent for p97 inhibition activity in a subject are provided herein.
Claims30
A method of measuring sensitivity of a subject to p97 inhibition, the method comprising:
- identifying a subject having a cancer, or a symptom thereof;
- and
- measuring an expression profile of oncoproteins in a biological sample obtained from the subject, wherein the measured expression profile of the oncoproteins differs from a normal expression profile from a healthy subject;
- wherein the oncoproteins comprise cell cycle oncoproteins or oncoproteins of a Cyclin D1-CDK4 or 6-RB1-E2F1 pathway;
- and
- wherein the oncoproteins of the Cyclin D1-CDK4 or 6-RB1-E2F1 pathway comprise Cyclin D1, CDK4, or ATF3.
A method of identifying a subject having a cancer with susceptibility to p97 inhibition, the method comprising:
- detecting a level of a protein in a biological sample obtained from the subject, wherein the protein is Securin, CyclinD1, MYC, Survivin, Emil, CDC20, Bub1, CDC25B, ORC6, GMNN, RRM2, CDK4, ATF3, TK1, DHFR, or an ortholog thereof, or a combination thereof.
A method of improving, ameliorating, or treating a cancer, the method comprising:
- detecting the genetic status, level, or expression of a cell cycle oncoprotein or a Cyclin D1-CDK4 or 6-RB1-E2F1 pathway oncoprotein in a subject;
- comparing the genetic status, level, or expression of the cell cycle oncoprotein or the Cyclin D1-CDK4 or 6-RB1-E2F1 pathway oncoprotein to the genetic status, level or expression of a cell cycle oncoprotein or a Cyclin D1-CDK4 or 6-RB1-E2F1 pathway oncoprotein in a healthy subject, wherein detection of an abnormal genetic status or a high level in the subject relative to the normal subject indicates the presence of a cancer in the subject;
- and
- administering to the subject an effective amount of an agent that inhibits p97 in the subject, wherein the agent that inhibits p97 is an inhibitory nucleic acid molecule, a p97 binding antagonist, a genetic tool, or a small molecule inhibitor;
- wherein the cancer or a symptom thereof is reduced after the administering, and
- wherein the Cyclin D1-CDK4 or 6-RB1-E2F1 pathway oncoprotein is Cyclin D1, CDK4, TK1, DHFR, or ATF3.
Dependencies are inferred from the claim text.