Dana-farber-cancer Institute Inc.

The Broad Institute, Inc.

Instituto Carlos Slim De La Salud, A.c.

Bayer Aktiengesellschaft

Steven Corsello

Philip Lienau

Ulf Bömer

Markus Berger

Anne Mengel

Detlev Sülzle

Volker Schulze

Todd R Golub

Wilhelm Bone

Clara Christ

Stefan Kaulfuss

Laura Furst

Jens Schröder

Ulrike Rauh

Roman Hillig

Rohith Nagari

Ryan Spangler

Christian Lechner

Amael Madec

Alisha Caliman

Adelaide Clara Faria Alvares De Lemos

Douglas Orsi

Mrinal Shekhar

Katarzyna Handing

David Mckinney

Jérémie Xavier G Mortier

Krzysztof Brzezinka

Kartarzyna Handing

Sven Christian

Rajesha Rupaimoole

Jérémie Mortier

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.

Cancers with loss of chromosome 16Q and/or low expression of metallothionein proteins

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.

Aryl hydrocarbon receptor (AHR) activator compounds as cancer therapeutics

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.

Tepoxalin targeting of ABCB1 overexpressing cancers

Growing community of inventors

Boston, MA, United States of America

Steven Corsello