公开(公告)号：US20220065864A1

公开(公告)日：2022-03-03

申请号：US17291458

申请日：2019-11-08

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Steven CORSELLO ,  Ryan SPANGLER ,  Rohith NAGARI ,  Todd GOLUB

IPC分类号： G01N33/574 ,  C12Q1/6886 ,  A61K31/415 ,  A61K45/06 ,  A61P35/00

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers that exhibit elevated expression and/or amplification of the ABCB1 (MDR1) transporter, optionally for reasons related to development of chemotherapeutic resistance having occurred during treatment with an initial chemotherapeutic drug. In particular, the instant disclosure provides for identification of a cancer as possessing elevated ABCB1 expression and/or exhibiting resistance to a non-tepoxalin chemotherapeutic drug, and selecting and/or administering tepoxalin, a tepoxalin derivative and/or metabolite thereof as a therapeutic agent for such a cancer and/or subject having or at risk of developing such a cancer. Methods and compositions for therapies that combine such tepoxalin or tepoxalin-related compounds with other cancer therapies and/or chemotherapeutic agents are also provided.

公开(公告)号：US20210147828A1

公开(公告)日：2021-05-20

申请号：US17148477

申请日：2021-01-13

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC.

发明人： Uri BEN-DAVID ,  Todd GOLUB ,  Rameen BEROUKHIM ,  Oana ENACHE ,  Veronica RENDO

IPC分类号： C12N15/10 ,  C12N9/22 ,  C12N15/11 ,  A61K35/13 ,  C12Q1/6883

摘要： Described herein are embodiments of methods to rationally design CRISPR-Cas system-based therapeutics and therapies based on expression of a DNA-damage response signature in a cell. In some embodiments, the methods include screening a set of CRISPR-Cas systems by expressing each CRISPR-Cas system in a test cell population and modifying one or more target sequences in the test cell population; screening in the test cell population for each CRISPR-Cas system and expression of a DNA-damage response signature; and selecting one or more CRISPR-Cas systems that do not result in expression of a DNA-damage response signature.

公开(公告)号：US20220017524A1

公开(公告)日：2022-01-20

申请号：US17293255

申请日：2019-11-14

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Steven CORSELLO ,  Ryan SPANGLER ,  Rohith NAGARI ,  Todd GOLUB ,  Amael MADEC

IPC分类号： C07D487/04 ,  C07D471/14 ,  A61K45/06

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of FOXA1 and/or FOXA1 gene targets, such as certain breast, liver and/or prostate cancers, including luminal and/or ER-positive forms of breast cancer. Three previously identified adenosine receptor antagonists, CGS-15943, MRS-1220 and SCH-58261, as well as furan ring moiety-possessing derivatives of CGS-15943 are specifically provided for killing cancer cells in a manner that appears to involve activation of the aryl hydrocarbon receptor (AHR) by such compounds. The instant disclosure therefore provides for selecting and/or administering CGS-15943, MRS-1220, SCH-58261 and/or a furan-possessing derivative of CGS-15943, MRS-1220 and/or SCH-58261 as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided

公开(公告)号：US20170240632A1

公开(公告)日：2017-08-24

申请号：US15519212

申请日：2015-10-16

申请人： THE BROAD INSTITUTE INC. ,  DANA-FARBER CANCER INSTITUTE, INC

发明人： David K. THOMAS ,  Todd GOLUB

IPC分类号： C07K16/28 ,  G01N33/68

CPC分类号： C07K16/2803 ,  C07K2317/34 ,  C07K2317/76 ,  C07K2317/92 ,  G01N33/6893 ,  G01N2800/10

摘要： The invention provides therapeutic, engineered protein/peptide compositions comprising e.g., RAGE antibodies, T-cell receptors to target a RAGE receptor (including soluble forms thereof) directly and/or via differential competition with one or more pre-cachexia and/or cachexia-associated RAGE ligands or markers.

公开(公告)号：US20220010383A1

公开(公告)日：2022-01-13

申请号：US17293381

申请日：2019-11-13

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Steven CORSELLO ,  Ryan SPANGLER ,  Rohith NAGARI ,  Todd GOLUB

IPC分类号： C12Q1/6886 ,  A61K31/145 ,  A61K31/166 ,  A61P35/00

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit arm-level loss of chromosome 16q, focal copy loss of 16q13 and/or low expression of metallothionein proteins, such as certain uterine, ovarian, gastroesophageal and lung cancers. Three known drugs, disulfiram, elesclomol and thiram, as well as certain disulfiram metabolites, are specifically provided for killing cancer cells characterized by arm-level loss of chromosome 16q, focal copy loss of 16q13 and/or low expression of metallothioneins. The instant disclosure therefore provides for selecting and/or administering disulfiram, elesclomol and thiram and/or active metabolites or derivatives of disulfiram, elesclomol and thiram as a therapeutic agent(s) to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.

公开(公告)号：US20220008457A1

公开(公告)日：2022-01-13

申请号：US17293375

申请日：2019-11-13

申请人： THE BROAD INSTITUTE, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  INSTITUTO CARLOS SLIM DE LA SALUD, A.C.

发明人： Steven CORSELLO ,  Ryan SPANGLER ,  Rohith NAGARI ,  Todd GOLUB

IPC分类号： A61K33/24 ,  A61P35/00

摘要： The present disclosure relates to compositions and methods for the diagnosis and treatment or prevention of cancers, particularly cancers that exhibit elevated expression of SLC26A2, such as certain ovarian, endometrial, brain, bone, and lung cancers, as well as melanoma. A previously identified vanadium-containing compound, bis(maltolato)oxovanadium(IV) (BMOV), specifically provided for killing of SLC26A2 expressing cancer cells in a SLC26A2-dependent manner. The instant disclosure therefore provides for selecting and/or administering BMOV and related vanadium-containing compounds as a therapeutic agent to target a cancer cell and/or subject having or at risk of developing a cancer. Methods and compositions for therapies that include such compounds are also provided.