Abstract:
Abstract: Despite great strides being achieved in improving cancer patients’ outcomes
through better therapies and combinatorial treatment, several hurdles still remain due to
therapy resistance, cancer recurrence and metastasis. Drug resistance, culminating in relapse
and metastatic disease continue to be associated with fatal disease. Cancer stem cells (CSCs)
are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis.
Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have
been further characterised in many cancers with data illustrating that CSCs display great
abilities to self-renew, withstand therapies due to enhanced epithelial to mesenchymal (EMT)
properties, enhanced expression of ABC membrane transporters, activation of several
survival signaling pathways and increased immune evasion DNA repair mechanisms. CSCs
also display great heterogeneity with the consequential lack of specific CSC markers
presenting a great challenge to their targeting. In this updated review we re-visit CSCs within
the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs.
These promising strategies include targeting CSCs-specific properties using small molecule
inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as
targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present
recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-
associated drug resistance and metastasis.
