Timeline of KRAS Inhibitors

Timeline of KRAS Inhibitors

After decades of efforts, scientists have made progress into targeting KRAS mutations in several malignancies.

In 1967, Ha-Ras and Ki-Ras retroviral transforming genes were discovered.

Their human counterparts, HRAS and KRAS, were discovered in 1982.

The relationship between KRAS and lung cancer was described in 1984, KRAS mutation in lung cancer has progressed.

Mutant KRAS is constitutively activated and leads to persistent downstream signaling and oncogenesis.

In 2013, improved understanding of KRAS biology and newer drug designing technologies led to the crucial discovery of a cysteine drug-binding pocket in GDP-bound mutant KRAS G12C protein.

In 2021, covalent inhibitors that block mutant KRAS G12C were successfully developed.

In May 2021, the US FDA granted accelerated approval to Sotorasib for the treatment of adults with advanced NSCLC with a KRAS G12C mutation.

Sotorasib was the first KRAS G12C inhibitor to be approved, with several more in the pipeline.