Cancer stem cells : the root of cisplatin resistance in non-small cell lung cancer

Abstract

Lung cancer is the leading cause of cancer-related death in Ireland and worldwide. Despite advances in anti-cancer therapies, the overall 5-year survival for non-small cell lung cancer (NSCLC) remains poor (<15%). As such, it is critical that new strategies are explored to overcome this cancer type. In the absence of specific treatable mutations such as EGFR and EML4-ALK, cisplatin-based doublet chemotherapy remains the gold standard treatment for the majority of NSCLC patients. These patients are therefore subject to significant toxicities and in many instances, without therapeutic gain. While understanding the mode of action of cisplatin is desirable in refining therapeutic approaches that may further enhance the anti-tumour activity of this drug, cisplatin continues to pose a number of significant challenges in the clinical setting. The selection of pre-existing resistant cells and the acquisition of resistance in tumour cells during the course of treatment with chemotherapy undermines its curative potential and has become a significant clinical challenge in the treatment of NSCLC patients. Since the discovery of cancer stem cells (CSCs) in haematopoietic cancers and other solid tumours, little is known to date regarding the biology of lung cancer stem cells. The existence of cancer stem cells within the tumour cell population may explain the ineffectiveness of current treatments in eradicating tumour cells. While conventional cytotoxic therapies may target the majority of cancer cells, residual lung cancer stem cells can regenerate a cancer cell population resulting in tumour relapse in patients following chemotherapy. As such, there is an increasing need to identify and develop new therapeutic targets for specifically eradicating this specific cell population. The overall aim of this study was to investigate the role of CSCs as the root of cisplatin resistance in NSCLC and to identify targetable entities to overcome such resistance ...