BET Inhibitor Combination Therapy for Cancer



This invention describes a method of treating cancer using the approach of combining inhibitors of BET and MEK or BRAF.  BET inhibitors target bromodomain-containing proteins, transcriptional regulators which control expression of genes essential for tumor growth.  Inhibitors of MEK and BRAF target the MAPK signaling cascade, a pathway frequently mutated in cancer.  There are several BET bromodomain inhibitors in early stages of clinical development in various cancer types including hematologic malignancies and NUT midline carcinoma.  MEK/BRAF inhibitors such as Mekinist and Taflinar are currently marketed as combination therapies to treat BRAF-positive metastatic melanoma and in late-stage clinical development to treat other tumor types such as NSCLC and colorectal cancer.

MSK inventors utilized a proprietary computational model to predict cellular responses to thousands of potential drug combinations; from this, promising combinations were subsequently tested in vitro to confirm cellular activity.  The combination of a bromodomain inhibitor (JQ1, targeting c-Myc) and either a MEK or BRAF inhibitor showed enhanced activity in a melanoma cell line compared to single agent BET/MEK/BRAF inhibitors.



  • Combination BET inhibitor therapy could potentially lead to improved responses in melanoma compared to single agent BET/MEK/BRAF therapy
  • Such a combination therapy approach could be applicable to several tumor types, particularly given that BET inhibitors target c-Myc, an oncogene overexpressed in up to 20% of cancers, including certain types of lung, breast, and colon cancers



According to the American Cancer Society, there were about 75,000 newly diagnosed cases of melanoma in the U.S. in 2015, with an estimated prevalence of ~30,000 patients, translating into a potential market size of $3B.  In 2014, total combined annual sales of Novartis’ MEK inhibitor Mekinist and BRAF inhibitor Taflinar in melanoma were $313M in the U.S./E.U.



Initial application of melanoma



U.S. Basic (14/722,768) and PCT application (PCT/US2015/032642), both filed on May 27, 2015



Chris Sander, PhD, formerly Chair and Laboratory Head, Computational Biology Program, Sloan Kettering Institute, MSK


Eileen Flowers, PhD, Licensing Manager, Tel: 646-888-1067, E-mail:

Stage of Development

In vitro