Cellular Senescence in Hepatocellular Carcinoma: The Passenger or the Driver?

Cells. 2022 Dec 29;12(1):132. doi: 10.3390/cells12010132.

Abstract

With the high morbidity and mortality, hepatocellular carcinoma (HCC) represents a major yet growing burden for our global community. The relapse-prone nature and drug resistance of HCC are regarded as the consequence of varying intracellular processes and extracellular interplay, which actively participate in tumor microenvironment remodeling. Amongst them, cellular senescence is regarded as a fail-safe program, leading to double-sword effects of both cell growth inhibition and tissue repair promotion. Particularly, cellular senescence serves a pivotal role in the progression of chronic inflammatory liver diseases, ultimately leading to carcinogenesis. Given the current challenges in improving the clinical management and outcome of HCC, senescence may exert striking potential in affecting anti-cancer strategies. In recent years, an increasing number of studies have emerged to investigate senescence-associated hepatocarcinogenesis and its derived therapies. In this review, we intend to provide an up-to-date understanding of liver cell senescence and its impacts on treatment modalities of HCC.

Keywords: cell-cycle arrest; liver cancer; senescence-associated secretory phenotype; senescence-targeting therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis
  • Carcinoma, Hepatocellular* / pathology
  • Cellular Senescence
  • Humans
  • Liver Neoplasms* / pathology
  • Neoplasm Recurrence, Local
  • Tumor Microenvironment

Grants and funding

This study is funded by the Young Talent Project of Changzhou Health Commission (grant no. CZQM2022007), the Youth Fund of Changzhou Health Commission (grant no. QN202121) and the Basic Application Project of Changzhou Science and Technology Bureau (grant no. CJ20220142). Xiurong Cai and Hanyang Liu are funded by the Chinese Scholarship Council Foundation (202008320386; 201806380041).