Diagnostic and therapeutic methods for cancer
The present invention provides diagnostic and therapeutic methods and compositions for cancer. The invention provides methods of determining whether an individual having a cancer is likely to respond to treatment comprising a pan-RAF dimer inhibitor and a MEK or PI3K inhibitor, methods of predicting responsiveness of an individual having a cancer to treatment comprising a pan-RAF dimer inhibitor and a MEK or PI3K inhibitor, methods of selecting a therapy for an individual having a cancer, and methods of treating an individual having cancer based on the presence of a biomarker of the invention (e.g., a KRAS activating mutation, e.g., a KRAS-G13D mutation, or an NRAS activating mutation).
1. A method of treating an individual having melanoma, the method comprising:
(a) screening a sample from the individual for a KRAS-G13D mutation, wherein the individual has been determined to have a KRAS-G13D mutation; and
(b) administering a therapeutically effective amount of a pan-RAF dimer inhibitor and a MEK inhibitor to the individual based on the presence of a KRAS-G13D mutation determined in step (a),
wherein the pan-RAF dimer inhibitor is HM95573 and the MEK inhibitor is cobimetinib (GDC-0973).
2. A method of treating an individual having a melanoma, the method comprising administering to the individual a therapeutically effective amount of a pan-RAF dimer inhibitor and a MEK inhibitor, wherein prior to treatment a sample from the individual has been screened for a KRAS-G13D mutation and the presence of a KRAS-G13D mutation in the sample has been determined, and wherein the pan-RAF dimer inhibitor is HM95573 and the MEK inhibitor is cobimetinib (GDC-0973).
3. The method of claim 1 , wherein screening comprises amplifying and sequencing all or a portion of the KRAS gene.
4. The method of claim 1 , wherein the sample is a tissue sample, a cell sample, a whole blood sample, a plasma sample, a serum sample, or a combination thereof.
5. The method of claim 2 , wherein the sample is a tissue sample, a cell sample, a whole blood sample, a plasma sample, a serum sample, or a combination thereof.