Abstract
Simple SummaryLung 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.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.
Highlights
Lung cancer is the 2nd most commonly diagnosed malignancy and remains the leading cause of cancer death based on Global Cancer Observatory (GLOBOCAN) 2020 estimates of cancer incidence and mortality [1]
This study found that the silencing of Forkhead box C1 (FOXC1) reduced cell differentiation 133 (CD133)+ cells, self-renewal ability, and expression of cancer stem cell (CSC)-related genes (OCT4, homeobox protein/transcription factor (NANOG), SRY-Box transcription factor 2 (SOX2), and ABCG2); increased cisplatin and docetaxel sensitivity; and reduced gefitinib resistance
Regulated A549 CSCs’ self-renewal property and their ability to initiate tumor through regulation of the miRNA-128; decreased cell proliferation and mediated apoptosis in drug-refractory A549 through regulation of vascular endothelial growth factor (VEGF)/PI3K/AKT signaling via miR-128/in vitro and in vivo
Summary
Lung cancer is the 2nd most commonly diagnosed malignancy and remains the leading cause of cancer death based on Global Cancer Observatory (GLOBOCAN) 2020 estimates of cancer incidence and mortality [1]. 30% of patients with NSCLC have localized disease at the time of diagnosis and undergo curative surgery (early stages, I–II) or, in selected cases, after induction therapies (locally advanced stage, IIIAN2), whereas, in advanced stages (IIIB and IV), resection is generally unfeasible In the latter, the treatment of choice is the use of platinum-based chemotherapy leading to an initial successful therapy [2], but, in most cases, patients develop secondary tumors that frequently cause lethal relapse [4]. CSCs are rare and constitute an insignificant proportion of cells within a tumor mass that are likely to cause cell heterogeneity, sustaining the CSC hypothesis [7] This model posits that CSCs give rise to highly proliferating progenitor and differentiated cells comprising the bulk of neoplastic tissues that define the histological type of cancer [8]. We provide evidence of the presence of CSCs, CSC-associated mechanisms of drug/treatment resiliency, the capacity of CSCs to escape immune control, and diverse CSC-inhibitory agents to provide a broader knowledge in the elimination of this pro-tumorigenic and therapyresistant cell subpopulation
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
