New Opportunities and Challenges to Defeat Cancer Stem Cells

Abstract

Cancer stem cells (CSCs) are a sub-population of cancer cells capable of self-renewal, proliferation, differentiation, plastic adaptation and immune regulation, thereby mediating tumorigenesis, metastasis and therapy resistance. CSCs are associated with cancer progression and clinical outcomes of cancer patients. Therefore successfully targeting CSCs is required to eradicate and cure cancer. Functional regulators of stem cell (stemness) signaling pathways in human cancers have brought new opportunities to target CSCs and reframe cancer-targeting strategies in clinical settings. However, challenges remain due to a lack of complete understanding of CSC plasticity/heterogeneity and limited efficacy of individual stemness inhibitors in cancer treatment. In this article, we review the CSC signaling pathways and the current state of CSC-targeting therapeutics in combinatory treatment in clinical trials.

ITGA2is a target of miR-206 promoting cancer stemness and lung metastasis through enhancedACLYandCCND1expression in triple negative breast cancer

“…Over the last two decades, human tumor cells with stem cell properties (stemness) have been identified and demonstrated to initiate tumorigenesis and accelerate progression, coupled with therapy resistance, immune evasion and distant metastases [5][6][7][8][9][10][11][12] . However, targeting cancer stemness has yet to be widely achieved in the cancer clinic and therefore demands a better understanding and identification of targetable stemness regulators.…”

“…However, targeting cancer stemness has yet to be widely achieved in the cancer clinic and therefore demands a better understanding and identification of targetable stemness regulators. While genetic and epigenetic aberrations are known to enable tumor plasticity and stemness 10,13 , we focuses on epigenetic regulation in cross talk with micro-environmental cues in this work.…”

Dichotomy of Notch signalling in regulating tumour immune surveillance

“…CSCs are generally recognized using surface immune markers. However, due to redundant expression of these markers, the precise identification of CSCs is still elusive …”

Enhanced Kat3A/Catenin transcription: a common mechanism of therapeutic resistance

“…For both CSC and SSC, there are multiple points of intersection and crosstalk, including feedback and feed forward loops, connecting the various signaling cascades that modulate "stemness" allowing for escape from driver directed therapeutics. These targets and therapies blocking these pathways are summarized in recent reviews [8,[30][31][32] .…”

“…Despite tremendous advances in targeted therapeutics and personalized medicine, which have significantly increased progression free survival, maximum clinical success as defined by overall survival or "cures", remain limited due to therapeutic resistance [2] . These resistance mechanisms can be attributed to a subpopulation of self-renewing, highly tumorigenic, drug-resistant cancer stem cell/ tumor initiating cell (CSC/TIC), in which therapeutic pressure leads to the selection of therapy resistant clone [3][4][5][6][7][8] .…”