Yingyun Wang

Keywords cholangiocarcinoma biliary tract cancer KRAS oncogene RAS(ON) multi-selective inhibitor targeted therapy therapy resistance drug combinations preclinical models Introduction The KRAS oncogene is one of the most broadly mutated oncogenes in humans and a key driver in lung, colorectal, and pancreatic cancer, the three most common causes of death by cancer in the US.1,2 KRAS mutations also occur in less prevalent, but equally fatal, cancers such as those of the biliary tract, esophagus,...

Abstract Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations. However, the impact of inhibiting RAS functions in normal tissues is not known. RMC-7977 is a highly selective inhibitor of the active (GTP-bound) forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants.