RESUMO
Colorectal cancer (CRC) is the third most diagnosed cancer and the second most deadly type of cancer worldwide. In late diagnosis, CRC can resist therapy regimens in which cancer stem cells (CSCs) are intimately related. CSCs are a subpopulation of tumor cells responsible for tumor initiation and maintenance, metastasis, and resistance to conventional treatments. In this scenario, colorectal cancer stem cells (CCSCs) are considered an important key for therapeutic failure and resistance. In its turn, mitochondria is an organelle involved in many mechanisms in cancer, including chemoresistance of cytotoxic drugs due to alterations in mitochondrial metabolism, apoptosis, dynamics, and mitophagy. Therefore, it is crucial to understand the mitochondrial role in CCSCs regarding CRC drug resistance. It has been shown that enhanced anti-apoptotic protein expression, mitophagy rate, and addiction to oxidative phosphorylation are the major strategies developed by CCSCs to avoid drug insults. Thus, new mitochondria-targeted drug approaches must be explored to mitigate CRC chemoresistance via the ablation of CCSCs.
RESUMO
Colorectal cancer (CRC) is ranked third most incident and second most deadly around the world, and even though treatments significantly developed over the years, overall survival remains low. This scenario has the contribution of cancer stem cells (CSC), a subpopulation of the heterogeneous tumor bulk, considered to be responsible for the tumor maintenance, conventional therapies resistance, metastasis, and recurrence. In this regard, hypoxia appears as an important component of tumor microenvironment and CSC niche, being associated with a worse prognosis. Therefore, it is vital the study of hypoxia influence on CSC phenotype in CRC. The aim of this mini-review article is to present a brief overview on this field. Recent articles discoursed about CSC molecular regulation, signalling pathways, methods for the study of the topic, as well as molecules and drugs capacity of inhibiting the interplay of hypoxia-CSC. Finally, the studies demonstrated important results, extensively accessing the topics of cellular and molecular regulation and therapeutic intervention, being morphology an area to be more explored.
