Dana-farber-cancer Institute Inc.

The Broad Institute, Inc.

Massachusetts Institute of Technology

Novartis Ag

Harvard College

University of Pittsburgh

The Brigham and Women's Hospital, Inc.

Massachusetts Eye and Ear Infirmary

Instituto Carlos Slim De La Salud, A.c.

Levi A Garraway

Caroline Emery

Feng Zhang

Aviv Regev

Eric Lander

Le Cong

Mark A Rubin

William R Sellers

Giordano Caponigro

Rajee Antony

Nikhil Wagle

Cory M Johannessen

Carlos Garcia-Echeverria

Orit Rozenblatt-Rosen

Francesca Demichelis

Jennifer Rubin Grandis

Sunkyu Kim

Asaf Rotem

Scott Delach

Itay Tirosh

Benjamin Izar

Zainab Jagani

David J Konieczkowski

Ann Marie Egloff

Nicholas Stransky

Aaron D Tward

Elizabeth Stover

Eva M Goetz

Rajeee Antony

Gregory Kryukov

Carlos García-Echeverría

Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

C-RAF mutants that confer resistance to RAF inhibitors

Described herein are compositions and methods of using single-cell RNA-sequencing to identify treatment resistance in patients with ovarian cancer. Also, described herein are compositions and methods for treatment targeting resistance in patients with ovarian cancer.

Compositions and methods for treating ovarian tumors

Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

MEK1 mutation conferring resistance to RAF and MEK inhibitors

Isolated mutant ERK polypeptides and nucleic acids encoding the mutant ERK polypeptides are provided. Methods of screening cancer-containing samples for an ERK polypeptide mutation that confers resistance to treatment with a first MAPK pathway inhibitor are provided. Methods of optimizing treatment of a subject having cancer and methods of identifying compounds useful in treating cancer are also provided.

ERK1 and ERK2 mutations that confer resistance to MAPK pathway inhibitors

A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.

Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy

The invention provides methods and devices for determining molecular signatures in a cancer that predict response to a MARPK pathway inhibitor and methods of use of such signatures.

Methods of identifying responses to map kinase inhibition therapy

The present invention provides methods related to the treatment of head and neck squamous cell carcinoma (HNSCC) and its associated premalignant lesions. In particular, the invention features methods which may specifically target HNSCC-associated genes and alter gene expression to treat or alleviate a symptom of HNSCC, or its related premalignant lesions. These methods may involve decreasing the function of an HNSCC-associated gene with aberrant gain-of-function; or increasing the function of an HNSCC-associated gene with aberrant loss-of-function.

Compositions and methods of treating head and neck cancer

The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of BRAF. In particular embodiments, the invention concerns mutations in a BRAF sequence that confer resistance to a BRAF inhibitor. Identification of such mutations in a BRAF sequence allows the identification and design of second-generation BRAF inhibitors. Methods and kits for detecting the presence of a mutant BRAF sequence in a sample are also provided.

Screening method for BRAF inhibitors

The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of MEK. In particular embodiments, the invention concerns mutations in a MEK sequence that confer resistance to a MEK inhibitor. Identification of such mutations in a MEK sequence allows the identification and design of second-generation MEK inhibitors. Methods and kits for detecting the presence of a mutant MEK sequence in a sample are also provided.

MEK mutations conferring resistance to MEK inhibitors

BRAF mutations conferring resistance to BRAF inhibitors

Described are methods for identifying single nucleotide polymorphism (SNPs) that are useful for analyzing genetic samples, and for using said SNPs to determine genetic identity of samples.

Methods for identifying and using SNP panels

Growing community of inventors

Newton, MA, United States of America

Levi A Garraway