Purpose: Covalent inhibitors of KRASG12C specifically target tumors driven by this form of
mutant KRAS, yet early studies show that bypass signaling drives adaptive resistance …

Purpose: SHP2 inhibitors offer an appealing and novel approach to inhibit receptor tyrosine
kinase (RTK) signaling, which is the oncogenic driver in many tumors or is frequently …

Ras is phosphorylated on a conserved tyrosine at position 32 within the switch I region via
Src kinase. This phosphorylation inhibits the binding of effector Raf while promoting the …

KRAS gain-of-function mutations occur in approximately 30% of all human cancers. Despite
more than 30 years of KRAS-focused research and development efforts, no targeted therapy …

The RAS pathway is one of the most frequently deregulated pathways in cancer. RAS
signals through multiple effector pathways, including the RAF/mitogen-activated protein …

Covalent inhibitors of KRASG12C have shown antitumor activity against
advanced/metastatic KRASG12C-mutated cancers, though resistance emerges and …

Across a broad range of human cancers, gain-of-function mutations in RAS genes (HRAS,
NRAS, and KRAS) lead to constitutive activity of oncoproteins responsible for tumorigenesis …

Mutations in RAS oncogenes are frequently observed in human cancers, and the mutations
result in activation of the RAS–RAF–MEK–ERK pathway, leading to cell proliferation and …

RAS mutations are frequent in human cancer, especially in pancreatic, colorectal and non-
small-cell lung cancers (NSCLCs),–. Inhibition of the RAS oncoproteins has proven difficult …

Although several covalent KRAS G12C inhibitors have made great progress in the treatment
of KRAS G12C-mutant cancer, their clinical applications are limited by adaptive resistance …