Page 154 - D. Cancer biology

[D. Cancer biology-99]

Drug-tolerant persister (DTP) cell subpopulations showing

Src signaling and migration related gene activation is critical

in ALK-positive lung cancer (NSCLC)

Yeonju Lee¹, So-young Kim¹

¹Biomedical Research Institution, Chonnam National University Hwasun Hospital, Jeonnam Hwasun 58128,

Republic of Korea

Anaplastic lymphoma kinase (ALK) fusion oncogenes occur in approximately 3-5% of non-small cell lung cancer
(NSCLC). The third-generation ALK inhibitor lorlatinib has demonstrated clinical activity. The aim of the present

study was to clarify the mechanisms underlying drug-tolerance cancer cell to ALK inhibitor in NSCLC. SNU-2292
(EML4-ALK, Variant 3a) cells were treated with lorlatinib every 3 days at a concentration of 100 nM, and cells on

day 9, 12 were achieved at ~90% confluence. The correlation between gene expression and ALK inhibitor resistance
in NSCLC cells were determined from Cancer Signaling Phospho AB Array kit (Ebiogen). Result of antibody array

was analyzed by ExDEGA v.2.0. The antibody array results were confirmed by western blot. SNU-2292 cell lines
treated with the ALK inhibitor lorlatinib (100nM), we observed activation of p-Src, p-cRaf, p-MEK and p-ERK

expression in 9, 12days. Moreover, the pSrc increase was associated with cell migration, survival and proliferation
effect on SNU-2292-DTP (lorlatinib tolerance persister). Our data suggest that Src signaling may be an effective

approach to the treatment of ALK-NSCLC with drug-tolerance to ALK inhibitors (Lorlatinib).