Last but not least, 16 and 22 HCC cases demonstrated markedly heterogeneous telomere lengths in tumor cells and CAFs within individual tumors (termed intratumor cell–cell heterogeneity). This heterogeneity may reflect inconsistent rates of telomere dynamics and variable reactivation of telomerase within subpopulations of cells due to variation in antioxidant protective effects, or differences in telomere preservation/extension mechanisms. Such intratumor heterogeneity was proposed as a major obstacle for curative therapy in HCC 3, 48, inviting new challenges in the molecular understanding of HCC 49.