Abstract: Provided herein are methods of treating a cancer in a patient wherein the patient has a KRAS G12C mutation, comprising administering to the patient a therapeutically effective combination of sotorasib and RMC-4630.

Abstract: The present disclosure relates to combination therapies for treating a RAS related disease or disorder (e.g., cancer). In particular, the present disclosure relates to methods of treating a RAS related disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a RAS(ON) inhibitor in combination with one or more additional therapeutic agents, pharmaceutical compositions comprising a therapeutically effective amounts of the same, kits comprising the compositions and methods of use therefor.

Abstract: Disclosed are compositions and methods relating to variant alpha-amylases. The variant alpha-amylases are useful, for example, for starch liquefaction and saccharification, for cleaning starchy stains in laundry, dishwashing, and other applications, for textile processing (e.g., desizing), in animal feed for improving digestibility, and for baking and brewing.

Abstract: Disclosed are compositions and methods relating to variant alpha-amylases. The variant alpha-amylases are useful, for example, for starch liquefaction and saccharification, for cleaning starchy stains in laundry, dishwashing, and other applications, for textile processing (e.g., desizing), in animal feed for improving digestibility, and for baking and brewing.

Abstract: The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Abstract: The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Abstract: Methods are provided herein for treating a subject having a disease or disorder associated with cells having a SHP2 mutation, e.g., an activating SHP2 mutation. The SHP2 mutation may cause resistance to a SHP2 inhibitor, e.g., an allosteric SHP2 inhibitor. Methods herein provide administering to the subject a therapeutically effective amount of a SOS1 inhibitor alone or in combination with an additional therapeutic agent.

Abstract: The present disclosure relates to combinations of inhibitors of SOS1 and inhibitors of mTOR useful in the treatment of diseases or disorders.

Abstract: The present invention is directed to compositions and methods of treating or preventing diseases or disorders with inhibitors of SHP2, alone, and in combination with other therapeutic agents such as RAS pathway inhibitors (e.g., MEK inhibitors); methods of establishing appropriate treatment plans for subjects based upon the expression of one or more biomarker indicative of SHP2 inhibitor sensitivity; and methods of determining sensitivity to a SHP2 inhibitor based on a phosphorylation status of SHP2.

Abstract: Disclosed are compositions and methods relating to variant alpha-amylases. The variant alpha-amylases are useful, for example, for starch liquefaction and saccharification, for cleaning starchy stains in laundry, dishwashing, and other applications, for textile processing (e.g., desizing), in animal feed for improving digestibility, and for baking and brewing.

Abstract: The present disclosure relates to combinations of inhibitors of SOS1 and inhibitors of RAS useful in the treatment of diseases or disorders.

Abstract: Disclosed are compositions and methods relating to variant alpha-amylases. The variant alpha-amylases are useful, for example, for starch liquefaction and saccharification, for cleaning starchy stains in laundry, dishwashing, and other applications, for textile processing (e.g., desizing), in animal feed for improving digestibility, and for baking and brewing.

Abstract: The present invention is directed to compositions and methods of treating or preventing diseases or disorders with inhibitors of SHP2, alone, and in combination with other therapeutic agents such as RAS pathway inhibitors (e.g., MEK inhibitors); methods of establishing appropriate treatment plans for subjects based upon the expression of one or more biomarker indicative of SHP2 inhibitor sensitivity; and methods of determining sensitivity to a SHP2 inhibitor based on a phosphorylation status of SHP2.

Abstract: The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Abstract: The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Abstract: The present invention is directed to compositions and methods of treating or preventing diseases or disorders with inhibitors of SHP2, alone, and in combination with other therapeutic agents such as RAS pathway inhibitors (e.g., MEK inhibitors); methods of establishing appropriate treatment plans for subjects based upon the expression of one or more biomarker indicative of SHP2 inhibitor sensitivity; and methods of determining sensitivity to a SHP2 inhibitor based on a phosphorylation status of SHP2.

Abstract: The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Abstract: The present disclosure provides methods of treating diseases or disorders related to mutations in the SHP2 gene using allosteric inhibitors of SHP2 and methods and diagnostic tests for identifying subjects susceptible or resistant to allosteric inhibitors of SHP2. In particular, the present disclosure provides allosteric inhibitor-sensitive mutations and allosteric inhibitor-resistant mutations of SHP2 for diagnostic and therapeutic use.

Abstract: The present invention is directed to compositions and methods of treating or preventing diseases or disorders with inhibitors of SHP2, alone, and in combination with other therapeutic agents such as RAS pathway inhibitors (e.g., MEK inhibitors); methods of establishing appropriate treatment plans for subjects based upon the expression of one or more biomarker indicative of SHP2 inhibitor sensitivity; and methods of determining sensitivity to a SHP2 inhibitor based on a phosphorylation status of SHP2.

Abstract: Disclosed are compositions and methods relating to variant alpha-amylases. The variant alpha-amylases are useful, for example, for starch liquefaction and saccharification, for cleaning starchy stains in laundry, dishwashing, and other applications, for textile processing (e.g., desizing), in animal feed for improving digestibility, and for baking and brewing.