These results strongly indicate that EX527-mediated inhibition of SIRT1 in KRASG12C lung cancer enhanced the efficacy of erlotinib treatment through reduced cell proliferation, enhanced DNA damage, and increased apoptotic cell death, suggesting that the inhibition of SIRT1 in combination with erlotinib treatment constitutes a potential therapeutic strategy for KRASMut lung cancer. Here, SIRT1 is linked to lung cancer.