Cancer is a serious global health concern as it accounts for about 9.6 million
deaths worldwide. Despite striking breakthroughs made in understanding, prevention,
and treatment of cancer, the mortality rate is still high and no permanent cure has been
found. The major concern is the lack of effective therapies against advanced metastasis.
Thus, there is a dire need to implement new treatment approaches to combat this
dreadful disease. Cancer stem cells (CSCs), being critical players of tumors can be the
potential target for therapy. Currently, cancer stem cell therapy is gaining much
attention from researchers because of its ability to target the CSCs, which are
responsible for tumor initiation, progression, metastasis, therapeutic resistance, and
recurrence. While most conventional treatment strategies target fast-growing tumor
cells, CSCs may remain in the latent stage for extended periods thereby escaping the
traditional therapies and leading to treatment resistance. Hence, specific targeting of the
tumor-initiating cells has become the heart of cancer research, aiming at the complete
elimination of malignancies. Major strategies against CSCs include targeting surface
CSC biomarkers, blockage of self-renewal signaling pathways (Wnt, Nanog,
Hippo/YAP, Notch, PTEN, Hedgehog, and/or STAT3), genetic targeting of CSCs, cell
therapy, RNA interference utilizing miRNAs. Based on this concept, the present
chapter summarizes the current strategies and the lead molecules which have found
their route to preclinical and clinical studies. Since the evolution of clinical trials
targeting CSCs holds a sanguine promise of affecting cancer medicine. This chapter
will further throw light on rapid advancement made in this field, shortcomings faced in
targeting CSCs, and several critical issues that are yet to be resolved.
Keywords: Apoptosis, Angiogenesis, Cancer recurrence, Cancer stem cells, CSC
biomarkers, CSC niche, CSC origin, Differentiation, Immunotherapy, Metastasis,
Mutation, Oncogenic signaling, Plasticity, Self renewal, Stemness, Targeted
therapy, Transformation, Treatment resistance, Tumorigenesis, VSELs.