A Slow-Cycling LGR5 Tumor Population Mediates Basal Cell Carcinoma Relapse After Therapy
October 2018
in “
Nature
”
Studysummary This study found that vismodegib promotes Basal cell carcinoma regression by inducing tumor differentiation but leaves a small population of quiescent cells that can drive relapse, which can be eliminated by adding a Wnt signaling inhibitor.
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The study demonstrated that a slow-cycling population of LGR5+ tumor cells in basal cell carcinoma (BCC) mediated relapse after vismodegib therapy. Researchers found that while vismodegib initially reduced tumor size by promoting differentiation, a small population of LGR5+ cells persisted and led to tumor regrowth upon treatment discontinuation. These cells were characterized by active Wnt signaling. Combining vismodegib with Wnt signaling inhibition or LGR5 lineage ablation effectively eradicated BCC, suggesting that targeting LGR5+ cells could be crucial for preventing BCC recurrence. The study involved multiple experiments using mouse models and human biopsies, highlighting the importance of addressing resistant cell populations to improve long-term treatment outcomes.
