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AssigneesMiltenyi Biotec GmbH, The Brigham and Women's Hospital, Inc.
InventorsAlan D. D'Andrea, Patrizia Vinciguerra, Stephen J. Elledge, Shuhei Matsuoka, Agata M. Smogorzewska, Kay O. Hofmann
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Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention identifies and characterizes the FANCI polypeptide as a vital component of the Fanconi anemia pathway and discloses inhibitors of FANCI and methods of using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.
A method of diagnosing or determining if a subject has cancer or is at increased risk of cancer, the method comprising testing a sample from the subject for the presence of FANCI-containing foci using an antibody or antigen binding fragment thereof specific for FANCI, wherein said presence of FANCI-containing foci is indicative of cancer or an increased risk of cancer in said subject.
A method of diagnosing or determining if a subject has cancer or is at increased risk of cancer, the method comprising testing a FANCI gene of the subject for the presence of a cancer-associated coding change, wherein said presence of one or more cancer-associated coding changes is indicative of cancer or an increased risk of cancer in the subject.
A method of determining if a subject has cancer, or is at increased risk of developing cancer, said method comprising the steps of:
A method of diagnosing or determining if a subject has Fanconi anemia or is at increased risk of developing Fanconi anemia, the method comprising testing a FANCI gene of the subject for the presence of a Fanconi anemia-associated coding change, wherein said presence of one or more Fanconi anemia-associated coding changes is indicative of Fanconi anemia or an increased risk of Fanconi anemia in the subject.
A method of determining if a subject has cancer, or is at increased risk of developing cancer comprising the steps of:
A method of predicting whether a subject with a neoplastic disorder will respond to a genotoxic anti-neoplastic agent comprising determining the size or number of FANCI-containing foci in a sample from the subject using an antibody or antigen binding fragment thereof specific for FANCI, wherein if the number or size of said foci is reduced relative to the number or size of said foci in a sample from a control subject, then the subject is predicted to respond to a genotoxic anti-neoplastic agent.
A method of predicting whether a subject with a neoplastic disorder will respond to a genotoxic anti-neoplastic agent comprising determining the degree of ubiquitination of FANCI polypeptide in a sample from the subject, wherein if the degree of ubiquitination of said FANCI polypeptide in the sample is reduced when compared with a sample from a control subject, then the subject is predicted to respond to a genotoxic anti-neoplastic agent.
A method of identifying a tumor that is sensitive to a genotoxic anti-neoplastic agent comprising determining the size or number of FANCI-containing foci in a sample from a test subject, wherein if the number or size of said foci is reduced relative to the number or size of said foci in a sample from a control subject, then the sample from the test subject is identified as a tumor sensitive to a genotoxic anti-neoplastic agent.
A method of identifying an inhibitor of a Fanconi anemia DNA repair pathway, comprising:
A method of identifying an inhibitor of a non-Fanconi anemia DNA repair pathway, comprising:
A method of screening for a cancer therapeutic, the method comprising the steps of:
A method of screening for a chemosensitizing agent, said method comprising the steps of:
A method of sensitizing a subject to treatment with a genotoxic anti-neoplastic agent, the method comprising administering an inhibitor of FANCI to a subject who is receiving a genotoxic anti-neoplastic agent but is resistant to said agent.
A method of sensitizing a subject to treatment with a genotoxic anti-neoplastic agent, the method comprising:
A method of predicting the efficacy of a therapeutic agent in a cancer patient, comprising the steps of:
An isolated polypeptide sequence comprising a polypeptide sequence selected from the group consisting of the mutant FANCI polypeptide sequence of BD0952 cells shown in FIG. 9 and a GST polypeptide fused to the N-terminal 200 amino acid residues of the FANCI polypeptide.
An anti-FANCI siRNA to a FANCI target selected from the group consisting of SEQ ID NO:
Dependencies are inferred from the claim text.