KRAS mutant lung cancer is the most prevalent molecular subclass of adenocarcinoma
(LUAD), which is a heterogenous group depending on the mutation-type which affects
not only the function of the oncogene but affects the biological behavior of the cancer
as well. Furthermore, KRAS mutation affects radiation sensitivity but leads also to
bevacizumab and bisphosphonate resistance as well. It was highly significant that
allele specific irreversible inhibitors have been developed for the smoking associated
G12C mutant KRAS (sotorasib and adagrasib). Based on trial data both sotorasib and
adagrasib obtained conditional approval by FDA for the treatment of previously treated
advanced LUAD. Similar to other target therapies, clinical administration of KRASG12C
inhibitors (sotorasib and adagrasib) resulted in acquired resistance due to various
genetic changes not only in KRAS but in other oncogenes as well. Recent clinical studies
are aiming to increase the efficacy of G12C inhibitors by novel combination strategies.
