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Topic: Cancer Stem Cells: Impact on Treatment

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

Anuradha Vaidya
Symbiosis School of Biomedical Sciences, Symbiosis International University, Symbiosis Knowledge Village, Pune 412115, India.
Correspondence to: Dr. Anuradha Vaidya, Symbiosis School of Biomedical Sciences, Symbiosis International University, Symbiosis Knowledge
Village, Pune 412115, India. E-mail: dydirector@ssbs.edu.in

It has been almost two decades, since the existence of cells, such that they inhibit the productive activation of
leukemic stem cells (LSCs) were first demonstrated effector T cells. [7]
in acute myeloid leukemia (AML) using xenogenic
transplant models. [1,2] Although LSCs were the first type Other than the intrinsic factors such as the signaling
of cancer stem cell (CSC) to be described experimentally, pathways and the very recently stated micro RNA
CSCs have been identified in a variety of malignancies (miR-126) that drives quiescence and self-renewal
and extensive efforts have been made to understand within the LSCs; extrinsic factors such as the tumour
[8]
and characterize specific biomarkers associated microenvironment also plays a central role in the
with the various types of cancers. However, it still progression of cancer. The microenvironment has been
[3]
remains unclear whether these transformed cells arise implicated as a source of chemoresistance and disease
as a result of the normal cells undergoing a malignant relapse. Recent advances strongly indicate that the
change or whether they are the differentiated malignant leukemic cells target the microenvironment to create an
cells that have re-acquired stem-like characteristics. environment that is more suitable for the progression
[4]
Irrespective of the conundrum regarding the origin of cancer. [9] In fact quiescence has been described as
of the LSCs, studies have highlighted that there exists a survival strategy adopted by CSCs to resist harsh
remarkable heterogeneity to the LSC compartment at environmental conditions and cytotoxic insults. [10]
both the cellular and molecular level. Such intratumoral
[5]
heterogeneity has been associated with the failure of many Thus, cancer stem cells are the “unscathed successors”
chemotherapeutic agents and progress to a refractory that progressively deteriorate the condition of the patient.
state, also known as the state of secondary resistance. [6] Their inherent quiescent “status quo” along with the
Furthermore acquired quiescence has offered the CSCs complex interplay of several factors (as those discussed
to evade being killed by conventional chemotherapy and above) contribute towards sustaining and propagating
radiotherapy, leading to cancer relapse and metastasis. [4] the malignant disease. Eradicating CSCs, the root of
cancer origin and recurrence, has therefore been thought
Cancer immune surveillance is considered to be as a promising approach to improve cancer survival or
an important host protection process to inhibit even to cure cancer patients. Nevertheless, a major
[11]
carcinogenesis and to maintain cellular homeostasis. It challenge thwarting the eradication of CSCs is that their
has been shown that deregulation of the tightly controlled identification and isolation has been hampered due to the
immune response may result in immune escape of CSCs, non-specificity of their cell surface biomarkers and also
[3]
and there has been a growing interest in understanding by the fact that the commonly used fluorescent markers
the mechanisms that regulate the immune modulatory are not stable, and hence do not allow tracking over an
properties of the CSCs in order to develop more effective extended period of time. [12]
therapy that can eradicate these quiescent cells. Some of
the signs of immune tolerance projected by CSCs include A study conducted by Gardane et al., [13] published
downregulation of positive co-stimulatory molecules, in this issue demonstrates that low concentrations of
higher expression of negative co-stimulatory molecules,
and secretion of soluble factors that induce regulatory T This is an open access article distributed under the terms of the Creative
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How to cite this article: Vaidya A. The quintessential quiescence
of cancer stem cells: a struggle towards better treatment. J Cancer
DOI: Metasta Treat 2016;2:243-4.
10.20517/2394-4722.2016.10
Received: 24-02-2016; Accepted: 29-03-2016.

©2016 Journal of Cancer Metastasis and Treatment ¦ Published by OAE Publishing Inc. 243