Therapy‐induced enrichment of putative lung cancer stem‐like cells

Abstract

Tumour drug resistance is a major issue in the management of lung cancer patients as almost all lung tumours are either intrinsically resistant or quickly develop acquired resistance to chemotherapeutic drugs. Cancer drug resistance has recently been linked, at least in part, to the existence of cancer stem-like cells (CSLCs), a small sub-population of cells within the tumour that possess stem-like properties. CSLCs are often isolated by fluorescence activated cell sorting (FACS) according to the expression of certain stem-like cell membrane markers. Conflicting results regarding the specificity of particular stem cell surface markers for isolating CSLCs have, however, been recently reported. Therefore, alternative strategies enabling the identification and study of CSLCs should be considered, particularly in tumour types where appropriate stem cell markers are not well established and validated, like in lung cancer. In this article, we review data indicating therapy-selection as a valid approach for putative lung CSLCs enrichment. We believe that this strategy would be determinant for correctly assessing and characterising the sub-populations of CSLCs that are able to survive chemo or radiotherapy regimens and, at the same time, also have the ability to recapitulate and sustain tumour growth. Using therapy-induced enrichment of CSLCs may, therefore, prove to be an extremely useful method for studying CSLCs and provide new clues regarding potential therapeutic targets for their efficient elimination, which will undoubtedly play a decisive role in improving lung cancer patients' survival. Lung Cancer and Therapy ResistanceOver the last decades, our understanding of human cancer development has greatly increased and much progress has been made regarding cancer therapy. Nevertheless, our ability to develop clinically effective therapies based on this knowledge has had limited success. 1 After an apparently successful initial therapy, many tumours often relapse in a more aggressive form than the original tumour. Lung cancer is the worldwide leading cause of cancer-related deaths and one of the most incurable cancers due to late presentation, disease relapse and low rate of curative therapy. 2 Indeed, after an apparent good response to initial therapy, lung cancer has a particularly poor prognosis with 5-year survival lower than 15%. 3 There are two main types of lung cancer, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). About 15% of lung tumours are SCLCs and arise in the

miR-17-92/p38α Dysregulation Enhances Wnt Signaling and Selects Lgr6+ Cancer Stem-like Cells during Lung Adenocarcinoma Progression

“…Cancer relapse after radiotherapy and chemotherapy is the essential reason for reduced survival (6). Previously, efforts have focused on investigating the cells and mechanisms involved in the resistance and later virulence of lung cancers after therapeutic treatments (7,8). Recent theories in cancer research consider the existence of cell populations with stem cell-like properties in many cancer types (9,10).…”

Side population cells from long-term passage non-small cell lung cancer cells display loss of cancer stem cell-like properties and chemoradioresistance

“…The CSC theory provides an attractive cellular mechanism counting for malignant progression and therapeutic resistance in lung cancer (5)(6)(7)(8)(9)(10). The current anticancer therapies often destroy the bulk of a tumor mass but fail to eradicate CSCs (3).…”

“…The current anticancer therapies often destroy the bulk of a tumor mass but fail to eradicate CSCs (3). Thus, tumor recurrence or metastasis occurs by resident CSCs subsequent to a primary therapeutic response or initial induction of tumor remission (6)(7)(8). Therefore, a better understanding of CSCs biology will be useful to explore more effective methods to destroy CSCs.…”

“…Previous studies revealed that numerous malignant tumors such as lung cancer, are composed of diverse cell types with distinct proliferative and differential capacities (5)(6)(7). Thus, the emerging reasonable explanation is the existence of a rare subpopulation of cells that appear to be cancer stem cells (CSCs), and which may contribute in certain cases to resistance to cancer therapy and relapse (6)(7)(8).…”

“…Thus, the emerging reasonable explanation is the existence of a rare subpopulation of cells that appear to be cancer stem cells (CSCs), and which may contribute in certain cases to resistance to cancer therapy and relapse (6)(7)(8). In fact, several studies have suggested that a stem-like subpopulation derived from lung cancer cell lines and tumor specimens was isolated by flow cytometry, according to the detection of side population (SP) phenotypes (5).…”