Therapy-induced enrichment of cancer stem-like cells in solid human tumors: Where do we stand?

Area of Science:

• Oncology
• Cancer Biology
• Stem Cell Research

Background:

• Tumor recurrence and metastasis remain significant challenges in cancer treatment.
• Acquired or intrinsic resistance of tumor cells to standard therapies is a major cause of treatment failure.
• Cancer stem cells (CSCs) with stem-like properties are implicated in therapeutic resistance and tumor relapse.

Purpose of the Study:

• To investigate the role of drug-tolerant cancer stem cells in therapeutic resistance.
• To explore the mechanisms underlying the transition of differentiated cells to stem-like states.
• To propose combined therapeutic strategies targeting both sensitive cells and CSC plasticity.

Main Methods:

• Review of existing research on cancer stem cell induction by conventional chemotherapeutics (e.g., doxorubicin, cisplatinum) and radiation.
• Analysis of signaling pathways (e.g., Notch, Hedgehog, Wnt, TGF-β, ERK, AKT) associated with stem cell self-renewal, drug efflux (ABC transporters), and survival.
• Evaluation of phenotypic plasticity in tumor cells.

Main Results:

• Conventional cancer therapies can induce drug tolerance and stem-like properties in cancer cells.
• Activation of specific self-renewal, drug efflux, and survival pathways promotes resistance and treatment failure.
• Phenotypic plasticity enables differentiated cells to transition into a stem-like state, conferring resistance.

Conclusions:

• Targeting cancer stem cells and their plasticity is crucial for overcoming therapeutic resistance.
• Combined therapeutic strategies that address both drug-sensitive tumor cells and CSCs' switching capacity can improve patient survival.
• This approach holds potential for better clinical outcomes and prevention of tumor recurrence.