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.本發明涉及組合物以及單獨使用SHP2抑制劑和使用SHP2抑制劑與其他 治療劑諸如RAS路徑抑制劑(例如MEK抑制劑)的組合治療或預防疾病或病症的方法;基於指示SHP2抑制劑敏感性的一種或多種生物標記的表現針對個體制定適當的治療計劃的方法;以及基於SHP2的磷酸化狀態確定對SHP2抑制劑的敏感性的方法。