Thursday, December 19, 2024

Identifying And Targeting Cancer Stem Cells

Here is a paper from several years ago demonstrating further identification of (colon) cancer stem cells, with information on targeting such cells for therapy.  Abstract:

The cancer stem cell (CSC) theory highlights a self-renewing subpopulation of cancer cells that fuels tumour growth. The existence of human CSCs is mainly supported by xeno-transplantation of prospectively isolated cells, but their clonal dynamics and plasticity remain elusive. Here, we demonstrate that human LGR5+ colorectal cancer cells serve as CSCs in growing cancer tissues. Lineage-tracing experiments with a CRISPR-Cas9-mediated LGR5-CreER knock-in allele reveal self-renewal and differentiation capacity of LGR5+ tumour cells. Selective ablation of LGR5+ CSCs in LGR5-iCaspase9 knock-in organoids leads to tumour regression, followed by tumour regrowth driven by re-emerging LGR5+ CSCs. KRT20-CreER marks differentiated cancer cells that constantly diminish in tumour tissues, while reverting to LGR5+ CSCs and contributing to tumour regrowth after LGR5+ CSC ablation. We also show that combined chemotherapy potentiates LGR5+ CSCs targeting. These data provide insights into the plasticity of CSCs and their potential as a therapeutic target in human colorectal cancer.

We'll be following further developments in this field.