Previously, Aurora A Kinase (ARUKA) has been shown to mediate adaptive resistance to KRASG12C inhibitors, and synergistic antitumor effects have been demonstrated when combining inhibition of the mitotic cell regulator, WEE1, with ARUKA inhibition. Jong Woo Lee, MD, PhD, Yale Cancer Center and Yale University School of Medicine, New Haven, CT, discusses a preclinical study into the inhibition of ARUKA with VIC-1911 on resistance to sotorasib in lung cancer. The antitumor effect of combining VIC-1911 with a WEE1 inhibitor, adavosertib, was also explored. Findings from the investigation linked ARUKA activation to both intrinsic and acquired resistance to sotorasib in KRASG12C-mutated lung cancer and show antitumor activity for AURKA inhibition in these settings. Thus, combining ARUKA with sotorasib inhibition may be a promising therapeutic approach to overcoming intrinsic resistance to KRASG12C inhibitors in lung cancer. This interview took place at the IASLC 2022 World Conference on Lung Cancer congress in Vienna, Austria.

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