Kalasekar Sharanya Maanasi, VanSant-Webb Chad H, Evason Kimberley J
Department of Pathology and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Cancers (Basel). 2021 Nov 3;13(21):5524. doi: 10.3390/cancers13215524.
Hepatocellular carcinoma (HCC) represents a leading cause of cancer-related death, but it remains difficult to treat. Intratumor genetic and phenotypic heterogeneity are inherent properties of breast, skin, lung, prostate, and brain tumors, and intratumor heterogeneity (ITH) helps define prognosis and therapeutic response in these cancers. Several recent studies estimate that ITH is inherent to HCC and attribute the clinical intractability of HCC to this heterogeneity. In this review, we examine the evidence for genomic, phenotypic, and tumor microenvironment ITH in HCC, with a focus on two of the top molecular drivers of HCC: β-catenin (CTNNB1) and Telomerase reverse transcriptase (TERT). We discuss the influence of ITH on HCC diagnosis, prognosis, and therapy, while highlighting the gaps in knowledge and possible future directions.
肝细胞癌（HCC）是癌症相关死亡的主要原因之一，但治疗起来仍然困难重重。肿瘤内基因和表型异质性是乳腺癌、皮肤癌、肺癌、前列腺癌和脑肿瘤的固有特性，肿瘤内异质性（ITH）有助于确定这些癌症的预后和治疗反应。最近的几项研究估计，ITH是HCC的固有特性，并将HCC的临床难治性归因于这种异质性。在本综述中，我们研究了HCC中基因组、表型和肿瘤微环境ITH的证据，重点关注HCC的两个主要分子驱动因素：β-连环蛋白（CTNNB1）和端粒酶逆转录酶（TERT）。我们讨论了ITH对HCC诊断、预后和治疗的影响，同时强调了知识空白和可能的未来方向。
