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

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.

Selenium Yeast and Fish Oil Combination Diminishes Cancer Stem Cell Traits and Reverses Cisplatin Resistance in A549 Sphere Cells

“…Consistent with the previously reported culture of sphere-growing lung cancer cells [ 34 ], these A549 sphere cells were highly enriched for CD133 than parental A549 cells ( Figure 1 B). Consistent with enriched CD133+ cells from human lung cancer cell lines [ 2 ], coexpression of elevated ABCG2 was observed in these spheres ( Figure 1 B). Besides ABCG2, the level of another chemoresistance driver, B-cell lymphoma-2 (Bcl-2) [ 35 ], in these sphere cells was also higher than in parental cells ( Figure 1 B).…”

“…After culture in a defined small-molecule-based serum-free medium in a nonadhesive culture system, floating spheres with round and smooth contours were successfully obtained from A549 (EGFR wild-type, KRAS-G12S) human lung adenocarcinoma cells ( Figure 1 A). To characterize their stemness, the expression of lung CSC markers, such as CD133 [ 2 ] and ABCG2 [ 33 ], was examined. Consistent with the previously reported culture of sphere-growing lung cancer cells [ 34 ], these A549 sphere cells were highly enriched for CD133 than parental A549 cells ( Figure 1 B).…”

“…The protein levels of lung CSC markers, such as CD133 [ 2 ] and ABCG2 [ 33 ], were examined to determine whether this synergistic apoptosis induction was accompanied by the suppression of CSC traits. As expected, elevated ABCG2 and CD133 in A549 sphere cells were suppressed by the Se-Y and FO combination ( Figure 4 A).…”

“…Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for approximately eighteen percent (1.8 million) of all cancer deaths [ 1 ]. Approximately 85% of lung cancers are non-small cell lung cancers (NSCLCs), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma [ 2 ]. The most dominant subtype is lung adenocarcinoma [ 3 ].…”

“…Therefore, effective therapeutics to eliminate CSC is urgently required. However, most conventional anticancer drugs fail to effectively eradicate CSCs [ 4 ], and some of them have been reported to foster CSC traits [ 2 , 5 , 6 , 7 ]. On the contrary, diverse natural products, including diet-derived nutrients, are known to suppress CSC traits and related signaling molecules, representing a cornucopia of CSC inhibitors [ 4 , 8 , 9 ].…”