Cancer stem cells and therapeutic perspectives

Area of Science:

• Cancer Biology
• Stem Cell Biology
• Epigenetics

Background:

• The cancer stem cell hypothesis posits that tumors are sustained by rare stem-like cells.
• Stem cells possess self-renewal and differentiation capabilities, making them potential origins of cancer due to accumulated mutations.
• This review explores evidence for cancer stem cells and the regulatory mechanisms governing their fate.

Purpose of the Study:

• To review the role of cancer stem cells in tumor maintenance and development.
• To discuss the mechanisms controlling stem cell fate, focusing on epigenetic regulators.
• To highlight the connection between Polycomb Group genes, stem cell biology, and cancer.

Main Methods:

• Literature review of existing evidence on cancer stem cells.
• Analysis of extrinsic and intrinsic circuitry controlling stem cell fate.
• Focus on Polycomb Group (PcG) genes, including Polycomb repressive complex (PRC) 1 and 2 components (Bmi1, SU(Z)12).

Main Results:

• Polycomb Group (PcG) genes, particularly PRC1 (Bmi1) and PRC2 (SU(Z)12), are vital for stem cell self-renewal and are upregulated in various human cancers.
• Bmi1 and SU(Z)12 are downstream targets of Sonic hedgehog (Shh) and Wnt signaling pathways, respectively.
• These findings link epigenetic regulators (PcG) with developmental signaling pathways in cancer.

Conclusions:

• Dysregulation of PcG genes is critical in cancer and stem cell biology.
• Understanding the interplay between PcG genes and signaling pathways is key to targeting cancer stem cells.
• Potential therapies targeting cancer stem cells include inhibitors of hedgehog signaling (e.g., cyclopamine), GSK3 (e.g., BIO), and beta-catenin signaling (e.g., exisulind, imatinib).