# US 2014/0194366 A1 · Ovarian cancer stem cells and methods of isolation and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0194366 A1 - Document ID: US20140194366A1 - Status: Published application - Kind: A1 - Application number: 14/123,551 - Filed: 2012-06-01 - Published: 2014-07-10 - Earliest claimed: 2011-06-03 - Assignees: The General Hospital Corporation - Inventors: Patricia K. Donahoe; David T. MacLaughlin; Jose Teixeira - Web page: https://patentgrep.com/patent/US20140194366A1 ## CPC - G01N 33/57545: of the ovaries - A61K 31/416: condensed with carbocyclic ring systems, e.g. indazole - A61P 35/00: Antineoplastic agents - G01N 33/5073: {Stem cells} - G01N 2333/70585: CD44 - G01N 2333/70596: Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705 - G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention generally relates to methods, assays, compositions and kits related to a subpopulation of ovarian cancer stem cells which are selected or enriched by chemotherapeutic agents and inhibited by MIS (Mullerian Inhibiting Substance) and MIS mimetics. In particular, the present invention relates to a population of CD44+/CD24+/EpCam+/ECad− subpopulation of ovarian cancer stem cells. The present invention also provides methods to screen a subject with ovarian cancer to identify if they have an ovarian cancer comprising CD44+/CD24+/EpCam+/ECad− ovarian cancer stem cells, and methods to identify and enrich or isolate for such ovarian cancer cell populations. ## Claims ### Claim 1 A method to identify an ovarian cancer stem cell in a population of cells, comprising measuring the expression of CD24, CD44, EpCam and E-Cadherin in a cell, wherein if a cell is positive for the expression of CD24, CD44, EpCam and negative for the expression of E-Cadherin, the cell is identified as an ovarian cancer stem cell. ### Claim at position 2 2-28. (canceled) ### Claim 29 (depends on 1) The method of claim 1, wherein the ovarian cancer stem cells are responsive to inhibition of proliferation by MIS or a mimetic thereof. ### Claim 30 (depends on 1) The method of claim 1, wherein the ovarian cancer stem cells are resistant to chemotherapeutic agents. ### Claim 31 (depends on 30) The method of claim 30, wherein the chemotherapeutic agent is selected from the group consisting of: dexorubicin, taxol, cisplatin, paclitaxel and derivatives thereof. ### Claim 32 (depends on 1) The method of claim 1, wherein the population of cells is in a biological sample, wherein the biological sample comprises any of the group consisting of: ovarian cells, ascites, ovarian cell line, ovarian cancer biopsy sample. ### Claim 33 An assay comprising: (a) contacting a biological sample from a subject with at least one detectable antibody specific to CD44, CD24, EpCam and Ecadherin; (b) washing the sample to remove unbound antibodies, (c) measuring the intensity of the signal from the bound, detectable antibody to CD44, CD24, EpCam and E-cadherin, (d) comparing the measured intensity of the signal of CD44, CD24, EpCam and Ecadherin to a reference value for each of CD44, CD24, EpCam and Ecadherin expression levels, and if there is a measured intensity of CD44, CD24, EpCam is at or increased relative for a reference value for CD44, CD24, EpCam and the measured intensity of Ecadherin is decreased relative to a reference value for Ecadherein, and (e) identifying the subject has having increased probability of having chemotherapeutic resistant ovarian cancer. ### Claim 34 (depends on 33) The assay of claim 33, wherein the biological sample comprises any cells from any one selected from the group consisting of: ovarian cells, ovarian cancer biopsy cells, primary ascites, ovarian cell line. ### Claim 35 A method of treating a subject with ovarian cancer comprising administering a pharmaceutically effective amount of MIS or a MIS mimetic to the subject having ovarian cancer, wherein the ovarian cancer is determined to comprise a population of the CD44+/CD24+/EpCam+/Ecad− cells, and wherein the subject is not administered an effective amount of a chemotherapeutic agent if said subject is determined to have CD44+/CD24+/EpCam+/ECad− cells. ### Claim 36 (depends on 35) The method of claim 35, wherein the MIS is recombinant human MIS (rhMIS) or a pro-hormone or homodimer thereof. ### Claim 37 (depends on 35) The method of claim 35, wherein a MIS mimetic is SP600125 or a derivative thereof. ### Claim 38 A method of determining if a subject is responsive to MIS or a MIS mimetic comprising assaying a biological sample from the subject for the presence of CD44+/CD24+/Epcam+/Ecad− cells, wherein MIS or a MIS mimetic is administered to a subject if CD44+/CD24+/EpCam+/Ecad− cells are present, and administering to the subject a chemotherapeutic agent if CD44+/CD24+/EpCam+/ECad− cells are absent. ### Claim 39 (depends on 38) The method of claim 38, wherein the population of cells is in a biological sample, wherein the biological sample comprises any of the group consisting of: ovarian cells, ascites, ovarian cell line, ovarian cancer biopsy sample. ### Claim 40 An isolated population of ovarian cancer stem cells, wherein the ovarian cancer stem cells are positive for the expression of CD24, CD44, EpCam and negative for the expression of E-Cadherin. ### Claim 41 (depends on 40) The population of claim 40, wherein the ovarian cancer stem cells are further positive for the expression of Lin28. ### Claim 42 (depends on 40) The population of claim 40, wherein the ovarian cancer stem cells are mammalian ovarian cancer stem cells. ### Claim 43 (depends on 42) The population of claim 42, wherein the mammalian ovarian cancer stem cells are human ovarian cancer stem cells. ### Claim 44 A method for screening potential ovarian cancer therapeutics which comprises: (f) growing CD44+/CD24+/EpCam+/ECad− ovarian cancer stem cells in the presence of a compound suspected as being a chemotherapeutic, (g) growing said CD44+/CD24+/EpCam+/ECad− ovarian cancer stem cell in the absence of said compound, (h) determining the rate of growth of said CD44+/CD24+/EpCam+/ECad− cells in the presence of said compound and the rate of said CD44+/CD24+/EpCam+/ECad− ovarian cancer cells in the absence of said compound, and (i) comparing the growth rate of said CD44+/CD24+/EpCam+/ECad− cells, wherein a slower rate of growth of said CD44+/CD24+/EpCam+/ECad− cell in the presence of said compound is indicative of a ovarian cancer therapeutic.