Oncogenic KRAS: Signaling and Drug Resistance

SIMPLE SUMMARY: KRAS is one of the oncogenic proteins and best well-known GTPase proteins. Although KRAS serves as regulation of cellular process, abnormal mutated and GTP-bound KRAS is highly expressed in human cancers. Understanding biological characteristics and precise signaling of KRAS proteins is essential for targeted cancer therapy. This review explains signal transduction and exploration of targeted anticancer by activated KRAS. ABSTRACT: RAS proteins play a role in many physiological signals transduction processes, including cell growth, division, and survival. The Ras protein has amino acids 188-189 and functions as GTPase. These proteins are switch molecules that cycle between inactive GDP-bound and active GTP-bound by guanine nucleotide exchange factors (GEFs). KRAS is one of the Ras superfamily isoforms (N-RAS, H-RAS, and K-RAS) that frequently mutate in cancer. The mutation of KRAS is essentially performing the transformation in humans. Since most RAS proteins belong to GTPase, mutated and GTP-bound active RAS is found in many cancers. Despite KRAS being an important molecule in mostly human cancer, including pancreatic and breast, numerous efforts in years past have persisted in cancer therapy targeting KRAS mutant. This review summarizes the biological characteristics of these proteins and the recent progress in the exploration of KRAS-targeted anticancer, leading to new insight.