Memorial Sloan Kettering Cancer Center

Sloan-kettering Institute for Cancer Research

Other

Hsc Research and Development Limited Partnership

Fred Hutchinson Cancer Center

Telios Pharmaceuticals, Inc.

Joan Massague

James M Roberts

Andrew C Koff

Kornelia Polyak

Adrienne Boire

Qing Chen

Michelle Letarte

Carmelo Bernabeu

Sela Cheifetz

Samuel J Danishefsky

Ouathek Ouerfelli

Guangli Yang

Thordur Oskarsson

Nicolas Lecomte

Gaorav P Gupta

Andy J Minn

Karuna Ganesh

Manuel Valiente Cortes

Manuel Valiente

Malcolm A Moore

Larry Norton

Peggy L Porter

Mong-Hong Lee

Malcom Moore

Swarnali Acharyya

Malcolm Moore

The present invention relates to methods and compositions for inhibiting metastatic spread of cancer and/or inhibiting progression of pre-existing metastatic disease in a subject using L1CAM inhibition.

Treating metastatic cancer and model systems for metastatic disease

The present invention relates to methods for treating brain metastasis by inhibiting gap junction functionality. It is based, at least in part, on the discovery that cancer cells expressing Protocadherin 7 and Connexin 43 form gap junctions with astrocytes that promote the growth of brain metastases, and that inhibition of Protocadherin 7 and/or Connexin 43 expression in cancer cells reduce progression of brain metastases. It is further based on the discovery that treatment with gap junction inhibitors tonabersat and meclofenamate inhibited progression of brain metastatic lesions and enhanced the anti-cancer activity of the conventional chemotherapeutic agent, carboplatin.

Methods for treating brain metastasis

The present invention relates to methods and compositions for modulating the blood CSF barrier and for diagnosing, preventing and/or treating leptomeningeal metastasis. In particular embodiments of the invention, the permeability of the blood CSF barrier is modulated by agonists or antagonists of Complement Component 3 (C3) or its receptor.

Modulating permeability of the blood cerebrospinal fluid barrier

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Migrastatins and uses thereof

A signature for breast cancer tissue derived from a patient is established that is indicative of the virulence and risk of lung metastasis by determining the expression levels to define a sample signature, and comparing this sample signature to a reference signature. This determination is used to define appropriate treatment and monitoring options for the patient. Risk of metastasis to the lung can be reduced by treatment with a therapeutic combination that either (1) contains a first agent effective to inhibit epiregulin activity and a second agent effective to inhibit activity of a protein selected from the group consisting of MMP1, MMP2 and PTGS2, or (2) contains a therapeutic agent or combination of agents effective to inhibit activity MMP1, MMP2 and PTGS2. Agents that inhibit the CXCL1 pathway also can be used individually or in combination with these combinations.

Method of predicting and reducing risk of metastasis of breast cancer to lung

A signature for breast cancer tissue derived from a patient is established that is indicative of the virulence and risk of lung metastasis by determining the expression levels to define a sample signature, and comparing this sample signature to a reference signature. The reference signature defines a standard expression level for each gene and a significant change direction, i.e., either overexpressed or underexpressed. A sample signature that differs from the reference signature in the significant change direction for a predetermined number of the genes tested is indicative of a significant risk of lung metastasis. This determination is used to define appropriate treatment and monitoring options for the patient. Risk of metastasis to the lung can be reduced by treatment with a therapeutic combination that either (1) contains a first agent effective to inhibit epiregulin activity and a second agent effective to inhibit activity of a protein selected from the group consisting of MMP1, MMP2 and PTGS2, or (2) contains a therapeutic agent or combination of agents effective to inhibit activity MMP1, MMP2 and PTGS2. Agents that inhibit the CXCL1 pathway also can be used individually or in combination with these combinations.

This invention relates, e.g., to a method for identifying an agent that inhibits a metastatic cell (e.g. that inhibits cancer metastasis), comprising measuring the amount of seeding of a tumor by a detectably labeled, metastatic cell, in a subject, in the presence and absence of a putative agent, wherein the amount of seeding by the metastatic cell is proportional to the metastatic potential of the cell, and wherein a significant amount of inhibition of the seeding by the putative agent indicates that the putative agent is effective to inhibit the metastatic cell (e, g, cancer metastasis). Also described are kits suitable for performing methods of the invention.

Assay for anti-metastatic agents

An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. in vitro assays for discovering agents which effect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative and hyperproliferative disorders are provided.

Isolated P27 protein, nucleic acid molecules encoding same, methods of identifying agents acting on same, and uses of said agents

An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. In vitro assays for discovering agents which affect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative disorders are provided.

Isolated p27 protein

The subject invention is directed to the discovery of a protein involved in regulation of cell-cycle progression, and includes reagents and methods related thereto.

Methods for determining isolated p27 protein levels and uses thereof

The subject invention provides an isolated protein having an apparent molecular weight of about 27 kD and capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. The subject invention further provides an isolated antibody and a purified preparation of polyclonal and monoclonal antibodies which are specifically immunoreactive with a p27 protein. The subject invention further provides a kit for detecting a p27 protein.

Growing community of inventors

New York, NY, United States of America

Joan Massague