Lung Cancer Stem Cells and Their Clinical Implications

It is now widely accepted that stem cells exist in various cancers, including lung cancer, which are referred to as cancer stem cells (CSCs). CSCs are defined in this context as the subset of tumor cells with the ability to form tumors in serial transplantation and cloning assays and form tumors at metastatic sites. Mouse models of lung cancer have shown that lung CSCs reside in niches that are essential for the maintenance of stemness, plasticity, enable antitumor immune evasion, and provide metastatic potential. Similar to normal lung stem cells, Notch, Wnt, and the Hedgehog signaling cascades have been recruited by the CSCs to regulate stemness and also provide therapy-driven resistance in lung cancer. Compounds targeting β-catenin and Sonic hedgehog (Shh) activity have shown promising anti-CSC activity in preclinical murine models of lung cancer. Understanding CSCs and their niches in lung cancer can answer fundamental questions pertaining to tumor maintenance and associated immune regulation and escape that appear important in the quest to develop novel lung cancer therapies and enhance sensitivity to currently approved chemo-, targeted-, and immune therapeutics.