Using PDOs and genetically engineered mouse tumor organoids, Alvarez-Varela et al. [26] demonstrated that a subset of LGR5+ CRC cells expressing the RNA-binding protein MEX3A adopts a latent chemoresistant state under suboptimal niche conditions (e.g., TGF-β exposure or EGF deprivation). Here, LGR5 is linked to colorectal carcinoma.