Impact of Cancer Stem Cells and Cancer Stem Cell-Driven Drug Resiliency in Lung Tumor: Options in Sight

SIMPLE SUMMARY: Lung cancer is still the most common cause of cancer death, worldwide with increasing incidence. In lung cancer management, chemotherapy alone, or combined with radiotherapy induces cell death of the tumor bulk, but not the drug-resistant cancer stem cells (CSCs) causing disease recurrence and, in some cases lead to patient death. This is due to the capacity of CSCs to self-renew and initiate tumor with high heterogeneity that adds complexity to conventional therapy. The reviewed literatures herein affirm the existence of this cell fraction in lung tumors including the CSC- related cellular and molecular mechanisms of drug resiliency. Several novel CSC inhibitors have been tested under in vitro and in vivo conditions, and in few cases in the clinical setting with encouraging results. Nevertheless, in depth investigation is essential to provide more comprehensive data as to the mode of action of these anti-CSC agents particularly, under the clinical setting. ABSTRACT: Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment strategies, there remains a pressing need to develop more efficient therapy to further improve the management of this disease. Cancer stem cells (CSCs) are considered the root of sustained tumor growth. This consensus corroborates the CSC model asserting that a distinct subpopulation of malignant cells within a tumor drives and maintains tumor progression with high heterogeneity. Besides being highly tumorigenic, CSCs are highly refractory to standard drugs; therefore, cancer treatment should be focused on eliminating these cells. Herein, we present the current knowledge of the existence of CSCs, CSC-associated mechanisms of chemoresistance, the ability of CSCs to evade immune surveillance, and potential CSC inhibitors in lung cancer, to provide a wider insight to drive a more efficient elimination of this pro-oncogenic and treatment-resistant cell fraction.