Methods and compositions for treating non-ERK MAPK pathway inhibitor-resistant cancers
AssigneeBiomed Valley Discoveries, Inc.
InventorsSaurabh Saha, Dean Welsch, Gary DeCrescenzo, Jeffrey James Roix
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Abstract
The present invention provides, inter alia, methods, pharmaceutical compositions, and kits for treating or ameliorating the effects of a cancer in a subject, which cancer is refractory or resistant to non-ERK MAPK pathway inhibitor therapy. Also provided are methods for identifying a subject having cancer who would benefit from therapy with an ERK inhibitor and methods for inhibiting phosphorylation of RSK in a cancer cell that is refractory or resistant to a non-ERK MAPK pathway inhibitor.
Claims12
A method for treating or ameliorating the effects of a cancer in a subject comprising:
- (a) identifying a subject with cancer that has become refractory or resistant to BRAF inhibitor therapy, MEK inhibitor therapy, or BRAF and MEK inhibitor therapy, comprising:
- (1) obtaining a biological sample from the subject;
- and
- (2) screening the sample to determine whether the subject has become resistant to an inhibitor therapy selected from the group consisting of BRAF inhibitor therapy, MEK inhibitor therapy, and combinations thereof,
- wherein the screening for a cancer that is refractory or resistant to BRAF inhibitor therapy comprises identifying (i) a switch between RAF isoforms, (ii) upregulation of RTK signaling, (iii) reactivation of mitogen activated protein kinase (MAPK) signaling, (iv) the presence of a MEK activating mutation, and combinations thereof;
- and
- (b) administering to the subject with said refractory or resistant cancer an effective amount of an ERK inhibitor, which is BVD-523 or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.