Covalent drugs have been used to treat diseases for more than a century, but tools that
facilitate the rational design of covalent drugs have emerged more recently. The purposeful …

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Significant
efforts have largely defined major genetic factors driving PDAC pathogenesis and …

KRAS is one of the most commonly mutated proteins in cancer, and efforts to directly inhibit
its function have been continuing for decades. The most successful of these has been the …

Patients with localized pancreatic ductal adenocarcinoma (PDAC) are best treated with
surgical resection of the primary tumour and systemic chemotherapy, which provides …

Abstract Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) is the most frequently
mutated oncogene, occurring in a variety of tumor types. Targeting KRAS mutations with …

After decades of efforts, we have recently made progress into targeting KRAS mutations in
several malignancies. Known as the 'holy grail'of targeted cancer therapies, KRAS is the …

Genetically engineered mouse models only capture a small fraction of the genetic lesions
that drive human cancer. Current CRISPR–Cas9 models can expand this fraction but are …

Although RAS was formerly considered undruggable, various agents that inhibit RAS or
specific RAS oncoproteins have now been developed. Indeed, the importance of directly …

Son of sevenless homologue 1 (SOS1) protein is universally expressed in cells and plays an
important role in the RAS signaling pathway. Specifically, this protein interacts with RAS in …

Activating mutations in KRAS are the most frequent oncogenic alterations in cancer. The
oncogenic hotspot position 12, located at the lip of the switch II pocket, offers a covalent …