Novel therapies of the KRAS-mutant lung cancer

Moldvay Judit (1,2), Tímár József (3)
(1) Országos Korányi Pulmonológiai Intézet, Budapest
(2) Szegedi Tudományegyetem Tüdőgyógyászati Klinika, Szeged
(3) Semmelweis Egyetem Patológiai, Igazságügyi és Biztosítás Orvostani Intézete, Budapest

KRAS mutant lung cancer is the most prevalent molecular subclass of adenocarcinoma, which is a heterogenous group depending on the mutation-type which affects not only the function of the oncogene but affects the biological behaviour 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 irreverzible inhibitors have been developed for the smoking associated G12C mutant KRAS. More importantly, two inhibitors (sotorasib and adagrasib) showed clinical activity in previously treated advanced stage NSCLC patients. Similar to other target therapies, clinical administration of G12CKRAS inhibitors (LumyKras, Krazati) 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.

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