The General Hospital Corporation

Jose Teixeira

Patricia K Donahoe

David T MacLaughlin

Eric Fynn-Thompson

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&#x2212; 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&#x2212; ovarian cancer stem cells, and methods to identify and enrich or isolate for such ovarian cancer cell populations.

Ovarian cancer stem cells and methods of isolation and uses thereof

Provided herein are pyrazoloanthrones or functional derivatives or analogs thereof to activate MIS receptor-mediated downstream effects in a cell. In particular, methods are provided to prevent and treat cancer that expresses MIS receptor type II (MISRII) by administering to a subject at least one pyrazoloanthrone or a functional derivative or analog thereof. Also provided herein are methods to lower plasma androgen levels in a subject, and/or for the treatment of a subject with a disease characterized by excess androgen, whereby the subject is administered at least one pyrazoloanthrone or a functional derivative or analog thereof. Also provided are methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent with a pyrazoloanthrone or a functional derivative or analog thereof that lowers the effective dose of the chemotherapeutic agent.

Pyrazoloanthrone and derivatives thereof for the treatment of cancers expressing MISRII

The present invention provides a method of treating a condition or disease characterized by an excess of one or more androgens, the method comprising administering an effective amount of MIS protein or nucleic acid encoding MIS to a patient. The present invention also provides a method of decreasing the level of one or more androgens to a level below the normal level, the method comprising administering an effective amount of MIS protein or nucleic acid encoding MIS to a patient. The methods of the present invention are particularly well-suited for the treatment of prostatic cancer, polycystic ovarian disease, benign prostatic hypertrophy, and precocious puberty.

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Boston, MA, United States of America

Jose Teixeira