Targeting of circulating hepatocellular carcinoma cells to prevent postoperative recurrence and metastasis

Abstract

Currently, the main treatment for hepatocellular carcinoma (HCC) involves the surgical removal of tumors or liver transplantation. However, these treatments are often not completely curative, as they are associated with a risk for postoperative recurrence and metastasis. Circulating tumor cells (CTCs) are increasingly recognized as the main source for recurrence and metastasis after radical hepatectomies are performed. Many studies have demonstrated the association between the presence of either pre- or postoperative CTCs and an increased risk for HCC recurrence. To improve the therapeutic outcome of HCC, a personalized, comprehensive and multidisciplinary approach should be considered, involving the application of appropriate diagnostic and therapeutic measures targeting HCC CTCs in different stages throughout the course of treatment. This article proposes some HCC CTC-based strategies for the treatment of HCC, including the monitoring of HCC CTCs before, during and after radical hepatectomy, therapeutic targeting of HCC CTCs, prevention of the generation and colonization of CTCs, as well as the use of CTC indexes for the selection of indications, prediction of prognoses, and planning of individualized therapeutic regimens. Innovation and technological development of therapies targeting CTCs, as well as their translation into clinical practice, will help to effectively reduce postoperative recurrence and metastasis, and significantly prolong the survival of HCC patients.

Donor interleukin 6 gene polymorphisms predict the recurrence of hepatocellular carcinoma after liver transplantation

“…Norris et al showed that hepatocytes could directly synthesize IL6 mRNAs and protein following hepatic stimuli, including partial hepatectomy [40]. Circulating tumor cells can lead to recurrence and metastasis of HCC after liver transplantation [41]. We speculate that donor hepatocytes alter not only local IL6 levels in the liver but also serum IL6 levels, both of which promote recurrence and metastasis after transplantation by acting on the circulating tumor cells.…”

Expression of cancer stem cell biomarkers as a tool for a correct therapeutic approach to hepatocellular carcinoma

“…Circulating biomarkers such as serum AFP, VEGF, HGF, and TGF-β are still preferred for prognostic prediction. Circulating tumor cells (CTCs) may reflect tumor aggressiveness and serve as a promising candidate for predicting relapse and metastasis [58]. However, their utility is limited by the rarity of CTCs in the peripheral blood even if recent technical findings have made it possible to detect CTCs in multiple tumor types, including breast cancer [59], lung cancer [60] and others [61,62].…”

Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells

“…As only patients with early-stage HCC are able to achieve optimal survival by radical hepatectomy or liver transplantation, the majority of patients are beyond curative intervention upon HCC diagnosis (1,2). Notably, existing alternative strategies, including chemotherapy and immunotherapy, have seldom elicited satisfactory responses in HCC (2,3).…”