Some of the deadliest cancers harbor mutations in the Kirsten Rat Sarcoma virus (KRAS) gene. The recent development of therapies that target and kill cancer cells with these mutations was heralded as a significant breakthrough. First identified in 1982, KRAS mutations are involved in approximately 25% of human cancers. The US FDA's approval of Amgen's sotorasib (LUMAKRAS) in May 2021 marks the first time that marketing authorization has been granted to a KRAS targeted therapy. 

This article provides an update on current treatment options for KRAS-driven tumors and outlines the latest development activities including ongoing clinical trials of key experimental drugs with data sourced from IQVIA Pipeline Link and the newly launched IQVIA Trial Link. 

Mode of action
The KRAS gene is an oncogene that encodes the KRAS protein, a GTPase transductor protein, which is part of the RAS/MAPK signaling pathway and provides instructions to cells to proliferate. The KRAS protein converts the GTP molecule into the GDP molecule and acts as a switch that is turned on and off by these molecules. The KRAS protein is activated by binding to a GTP molecule and inactivated when it converts GTP to GDP as it does not relay signals to the cells when the protein is bound to GDP. Oncogenes have the potential to cause normal cells to become cancerous when mutated. The KRAS gene is a member of the RAS family of oncogenes, which also includes the Harvey Rat Sarcoma virus (HRAS) and Neuroblastoma Rat Sarcoma virus (NRAS) genes. These proteins play important roles in cell division, cell differentiation and apoptosis of cells. The activation of KRAS mutation occurs when there is a shift in balance of the KRAS protein to a GTP-loaded active state, which triggers tumor proliferation.

Discover more by downloading the article. It covers treatment options, next-generation drugs for KRAS-mutant tumors, clinical trial analysis, and highlights early-stage KRAS inhibitors.