Targeting cancer stem cell pathways for lung cancer therapy

Purpose of review The unique properties of cancer stem cells (CSCs) make lung cancer untargetable for quite an extended period. The functional mechanism of this cell type has been illustrated step by step. However, the outcomes of lung cancer patients are still lower than expected clinically. The attempts made by scientists to make challenge history against stemness maintenance of lung cancer cells and their druggable targets are worth elucidating. Recent findings Many agents, including the Bispecific T-cell engager (BiTE) and AMG 119 targeting DLL3-positive cells, are a tremendous breakthrough in the preclinical and clinical treatment of SCLC. More studies focus on targeting CSCs to overcome TKI resistance in NSCLC. The combo targeting of CSC and the immune microenvironment can favor the treatment of lung cancer patients. Summary The current review elucidates the characteristics and related regulating pathways of lung CSCs from essential to preclinical research. We retrospectively introduce an update on the clinical development of therapeutics targeting CSC-associated developmental signaling pathways and discuss the opportunities to target CSC–immune interactions in lung cancer.