Dana-farber-cancer Institute Inc.

The Brigham and Women's Hospital, Inc.

Oregon Health & Science University

Genetics Institute, Inc.

Children's Medical Center Corporation

Whitehead Institute for Biomedical Research

Alan D D'Andrea

Kalindi Parmar

Markus Grompe

Toshiyasu Taniguchi

Nathanael Schiander Gray

Gregory D Cuny

Min Huang

Gordon G Wong

Marcie A Glicksman

Sara Jean Buhrlage

Simon S Jones

Jun Xian

Ross L Stein

David Wilson

Haojian Zhang

Kah Suan Lim

April Case

Jia Zhou

Raphael Ceccaldi

Yuan Zhu

David T Weaver

Edward A Fox

Cynthia Timmers

Richard Kennedy

The disclosure relates to methods for treating cancers (e.g., cancers having a BRCA1 and/or BRCA2 mutation(s)) by administering to the subject an effective amount of a ubiquitin-specific protease 1 (USP1) inhibitor.

Methods of treating cancers having a BRCA1 and/or BRCA2 mutation(s)

The present application provides, in some aspects, methods of treating cancers, such as homologous recombination (HR)-deficient cancers. In some embodiments, the disclosure provides a method for treating cancer by administering to a subject a compound of Formula (I):(I), or a pharmaceutically acceptable salt thereof.

Compounds and methods for treating cancer

The present invention provides methods of treating, preventing or delaying the onset of bone marrow failure in Fanconi Anemia patients.

Compositions and methods of treating Fanconi Anemia

The present invention provides methods of increasing the efficiency of genome editing.

Methods for enhancing the efficiency of gene editing

Methods of treating cancers

The present application provides, in some aspects, methods of treating cancers, such as homologous recombination (HR)-deficient cancers. In some embodiments, the disclosure provides a method for treating cancer by administering to a subject a compound of Formula (I):(I), or a pharmaceutically acceptable salt thereof. 

This present invention compositions and methods of treating cancer and methods of accessing/monitoring the responsiveness of a cancer cell to a therapeutic compound.

Treating cancer deficient in FANCA, FANCD2, FANCE, or FANCG with an ATM inhibitor

Provided are small molecule inhibitors of ubiquitin specific protease 1 (USP1) activity and methods for their use in treating and characterizing cancers. The small molecule USP1 inhibitors of the invention are particularly useful in the treatment of cancers that are resistant to DNA cross-linking agents.

Small molecule inhibitors of USP1 deubiquitinating enzyme activity

The present invention provides methods of treating, preventing or delaying the onset of bone marrow failure in Fanconi Anemia patients comprising administering to the patient a composition comprising a neutralizing anti-TGF-beta antibody, e.g. fresolimumab or 1D11.

Anti-TGF-beta antibody for the treatment of fanconi anemia

Provided are small molecule inhibitors of ubiquitin specific protease 2, 8 and 12 (USP2 and USP8 and USP12) activity and methods for their use in treating cancers. The small molecule inhibitors of the invention are particularly useful in the treatment of non-small cell lung cancers that are resistant to tyrosine kinase inhibitors and in the treatment of prostate cancer that is resistant to AR inhibitor therapy. 

Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, and probes and primers are provided for screening patients in genetic-based tests and for diagnosing Fanconi Anemia and cancer. The FANCD2 gene can be targeted in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the monoubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact Fanconi Anemia/BRCA pathway.

Methods and compositions for the diagnosis of cancer susceptibilities and defective DNA repair mechanisms and treatment thereof

Disclosed herein are methods and compositions for the treatment of cancer. In particular, the present invention discloses inhibitors of the Fanconi anemia pathway and methods using same. Such inhibitors are useful in inhibiting DNA damage repair and can be useful, for example, in the treatment of cancer.

Compositions and methods for the treatment of cancer

The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.

Growing community of inventors

Winchester, MA, United States of America

Alan D D'Andrea