Cancer stem cells: in the line of fire

Area of Science:

• Oncology
• Cell Biology
• Cancer Research

Background:

• Tumors often contain cancer stem cells (CSCs) that are self-renewing and drive tumor expansion.
• CSCs are hypothesized to reside at the apex of a hierarchical tumor organization.
• Stemness may be a fluid trait, with cells potentially switching between stem and non-stem states.

Purpose of the Study:

• To review the mechanisms underlying cancer stem cell (CSC) resistance to radiotherapy and chemotherapy.
• To outline strategies for the effective eradication of CSCs.

Main Methods:

• Review of existing literature on cancer stem cell biology and treatment resistance.
• Discussion of key molecular determinants of CSC resistance, including ABC transporters, ALDH activity, signaling pathways, DNA damage response, hypoxia, and quiescence.

Main Results:

• CSCs exhibit significant resistance to conventional cancer therapies.
• Key factors contributing to CSC resistance include ABC transporters, aldehyde dehydrogenase (ALDH) activity, intracellular signaling, DNA damage response, hypoxia, and proliferative quiescence.

Conclusions:

• Targeting CSC self-renewal pathways (Wnt, Notch, Hedgehog), ALDH activity, and ABC transporters are potential therapeutic strategies.
• Blocking epithelial-mesenchymal transition (EMT), employing differentiation therapy, and targeting the CSC niche are also promising approaches for CSC eradication.