Massachusetts Institute of Technology

Dana-farber-cancer Institute Inc.

The Broad Institute, Inc.

Benjamin Izar

Aviv Regev

Orit Rozenblatt-Rosen

Asaf Rotem

Livnat Jerby

Levi A Garraway

Itay Tirosh

Elizabeth Stover

The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The novel gene signatures predict overall survival in cancer and can be targeted therapeutically. Specifically, disclosed is a resistance program identified by a comprehensive single-cell profiling study in melanoma patients, which was validated in two large validation cohorts. Using a large-scale in silico prediction, CDK4/6 inhibitors were identified as a class of drugs that may reverse this resistance program. These predictions were validated in melanoma cell lines, patient-derived co-culture models, and melanoma in vivo models, which show that the combination of abemaciclib and immune checkpoint blockade (ICB) overcome intrinsic drug resistance. The present invention provides for detecting an immunotherapy resistance signature and modulating the signature with CDK4/6 inhibition. Also provided is a novel phased immunotherapy and CDK4/6 inhibitor combination therapy regimen.

Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer

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

The subject matter disclosed herein is generally directed to detecting and modulating novel gene signatures for the treatment and prognosis of cancer. The novel gene signatures predict overall survival in cancer and can be targeted therapeutically.

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Boston, MA, United States of America

Benjamin Izar