Cancer Sci. 2020 Jul 20. doi: 10.1111/cas.14569. Online ahead of print.
ABT-263 (Navitoclax) is one of the BH3-mimetic drugs targeting anti-apoptotic B-cell lymphoma-2 (BCL-2) family proteins, including BCL-2, BCL-xL, and BCL-w, thereby inducing apoptosis. In small cell lung cancer (SCLC) cells, the response to ABT-263 is associated with the expression of the myeloid cell leukemia-1 (MCL-1) protein. However, the efficacy of ABT-263 in non-small cell lung cancer (NSCLC) has not been thoroughly evaluated. In addition, there are currently no established biomarkers
predicting the efficacy of ABT-263 treatment in NSCLC. We screened a panel of different NSCLC cell lines and found that ABT-263 inhibited cell proliferation and induced apoptosis in Calu-1, Calu-3, and BID007 cells. Inconsistent with previous reports on SCLC, low levels of MCL-1 did not predict the response to ABT-263 in NSCLC cells. However, we found that the intracellular levels of reactive oxygen species (ROS) in cancer cells were associated with the sensitivity to ABT-263 in NSCLC cells. We also showed that increasing the level of intracellular ROS could enhance the sensitivity to ABT-263 in NSCLC cells. In summary, we propose that the intracellular levels of ROS can be used as a potential novel biomarker for predicting a response to ABT-263 in NSCLC. Furthermore, we show some evidence supporting the further assessment of ABT-263 as a new therapeutic strategy in patients with NSCLC combined with agents regulating ROS levels. We believe that our findings and follow-up studies on this matter would lead to novel diagnostic and treatment strategies in patients with NSCLC.