The RTK-RAS-MAPK pathway is the most frequently altered signaling pathway at the rate of 46% across all cancer types. KRAS alternation is the top common event across all samples at 9%, and particularly predominant in pancreatic cancer (72%), colon cancer (69%) and lung cancer (33%). Oncogenic KRAS not only initiates tumorigenesis, but is also required for tumor maintenance, implying KRAS as an ideal therapeutic target for cancer treatment. Due to great advances of targeting RAS achieved in the past decade, KRAS can be druggable now by various methods. However, drug resistance occurs as expected, emphasizing that to overcome KRAS targeted therapy (KRASi) resistance is the key for favorable disease control.
Current projects focus on understanding tumor cell autonomous and non-autonomous KRASi resistance mechanisms, including exploring resistance-associated immune cells in the tumor microenvironment and dissecting how cell fate transition regulates KRASi resistance via epigenetic modulation.