# US 7,745,165 B2 · Phosphatase associated with metastasis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,745,165 B2 - Document ID: US7745165B2 - Status: Granted - Kind: B2 - Application number: 10/868,658 - Filed: 2004-06-16 - Published: 2005-03-03 - Granted: 2010-06-29 - Earliest claimed: 2001-10-09 - Assignees: The John Hopkins University - Inventors: Bert Vogelstein; Kenneth W. Kinzler; Saurabh Saha; Alberto Bardelli - Web page: https://patentgrep.com/patent/US7745165B2 ## CPC - C12N 9/16: acting on ester bonds (3.1) - A61P 35/00: Antineoplastic agents - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) - C12Q 2600/112: Disease subtyping, staging or classification - C12Q 2600/136: Screening for pharmacological compounds - C12Q 2600/158: Expression markers - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Among the genes identified, in a comparison of the global gene expression profile of metastatic colorectal cancer to that of primary cancers, benign colorectal tumors, and normal colorectal epithelium, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. In three of twelve metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions. ## Claims ### Claim 1 A method to identify candidate drugs useful for treating advanced or metastatic tumors, comprising: determining the ability of a test compound to inhibit PRL-3 activity; identifying a test compound which inhibits PRL-3 activity as a compound potentially useful in treating advanced or metastatic tumors; testing the compound which inhibits PRL-3 activity for the ability to inhibit growth of cancer cells in vitro, wherein the cancer cells are selected from the group consisting of gastrointestinal, colorectal, and cancer cells that have metastasized to the liver. ### Claim 2 (depends on 1) The method of claim 1 wherein the step of determining utilizes DiFMuP (6,8-difluoro-4-methylumbelliferyl phosphate) as a substrate of PRL-3 in an enzyme assay. ### Claim 3 (depends on 1) The method of claim 1 wherein the step of determining utilizes p130cas as a substrate of PRL-3 in an enzyme assay. ### Claim 4 (depends on 1) The method of claim 1 wherein the cancer cells are gastrointestinal cancer cells. ### Claim 5 (depends on 1) The method of claim 1 wherein the cancer cells are colorectal cancer cells. ### Claim 6 (depends on 1) The method of claim 1 wherein the cancer cells are cancer cells that have metastasized to the liver. ### Claim 7 (depends on 1) The method of claim 1 wherein the test compound is tested for its ability to inhibit PRL-3 relative to an enzyme selected from the group consisting of PRL-2 and PRL-1. ### Claim 8 (depends on 1) The method of claim 1 wherein the step of determining uses an enzyme assay. ### Claim 9 (depends on 1) The method of claim 1 wherein the step of determining uses a substrate of PRL-3 selected from the group consisting of DiFMuP (6,8-difluoro-4-methylumbelliferyl phosphate), p130cas and histone 2B, in an enzyme assay. ### Claim 10 A method to identify candidate drugs useful for treating advanced or metastatic tumors, comprising: determining the ability of a test compound to inhibit PRL-3 activity; identifying a test compound which inhibits PRL-3 activity as a compound potentially useful in treating advanced or metastatic tumors; and testing in vivo the compound which inhibits PRL-3 for the ability to inhibit progression of a tumor in an experimental animal, wherein the tumor is selected from the group consisting of gastrointestinal cancer and colorectal cancer. ### Claim 11 (depends on 10) The method of claim 10 wherein the tumor is a gastrointestinal tumor. ### Claim 12 (depends on 10) The method of claim 10 wherein the tumor is a colorectal tumor. ### Claim 13 (depends on 10) The method of claim 10 wherein the step of testing comprises administering the compound to the experimental animal. ### Claim 14 (depends on 10) The method of claim 10 wherein the step of determining uses an enzyme assay. ### Claim 15 (depends on 10) The method of claim 10 wherein the step of determining uses a substrate of PRL-3 selected from the group consisting of DiFMuP (6,8-difluoro-4-methylumbelliferyl phosphate), p130cas, and histone 2B, in an enzyme assay. ### Claim 16 A method to identify candidate drugs useful for treating advanced or metastatic tumors, comprising: determining the ability of a test compound to inhibit PRL-3 activity; identifying a test compound which inhibits PRL-3 activity as a compound potentially useful in treating advanced or metastatic tumors; and testing in vivo the compound which inhibits PRL-3 for the ability to inhibit metastasis of a colorectal tumor in an experimental animal. ### Claim 17 (depends on 16) The method of claim 16 wherein the step of testing comprises administering the compound to the experimental animal. ### Claim 18 (depends on 16) The method of claim 16 wherein the step of determining uses an enzyme assay. ### Claim 19 (depends on 16) The method of claim 16 wherein the step of determining uses a substrate of PRL-3 selected from the group consisting of DiFMuP (6,8-difluoro-4-methylumbelliferyl phosphate), p130cas, and histone 2B, in an enzyme assay.