The quintessential quiescence of cancer stem cells: a struggle towards better treatment

Received: 24-02-2016; Accepted: 29-03-2016. It has been almost two decades, since the existence of leukemic stem cells (LSCs) were first demonstrated in acute myeloid leukemia (AML) using xenogenic transplant models.[1,2] Although LSCs were the first type of cancer stem cell (CSC) to be described experimentally, CSCs have been identified in a variety of malignancies and extensive efforts have been made to understand and characterize specific biomarkers associated with the various types of cancers.[3] However, it still remains unclear whether these transformed cells arise as a result of the normal cells undergoing a malignant change or whether they are the differentiated malignant cells that have re-acquired stem-like characteristics.[4] Irrespective of the conundrum regarding the origin of the LSCs, studies have highlighted that there exists remarkable heterogeneity to the LSC compartment at both the cellular and molecular level.[5] Such intratumoral heterogeneity has been associated with the failure of many chemotherapeutic agents and progress to a refractory state, also known as the state of secondary resistance.[6] Furthermore acquired quiescence has offered the CSCs to evade being killed by conventional chemotherapy and radiotherapy, leading to cancer relapse and metastasis.[4]